Microplastics have become a defining environmental signature of modern life, turning up in oceans, soil, food, drinking water, and even the air. But their biological fate inside the human body remains far less understood. A new study suggests that these particles may be doing more than simply passing through. Instead, they may be accumulating in one of the body’s most overlooked fluids—bile—and leaving behind measurable cellular damage that could shape future thinking about environmentally driven biliary injury and long‑term health effects. As the authors noted in their abstract, “the long-term accumulation patterns and chronic toxic effects of microplastics within the human biliary system are largely unknown,” underscoring the need for deeper investigation into how these particles behave in the enterohepatic circulation.
Researchers from the Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital), Sun Yat-sen University, Guilin Medical University, and collaborating institutions reported the findings in Environmental Science and Ecotechnology. Their study, “Microplastics accumulate in human bile and drive cholangiocyte senescence,” provides the first direct evidence that microplastics are not only present in bile but may also contribute to mitochondrial dysfunction and premature aging in cholangiocytes, the epithelial cells that line the bile ducts.
The team collected bile from 14 surgical patients (five without gallstones and nine with gallstones) and used a multimodal analytical approach—pyrolysis–gas chromatography–mass spectrometry, laser direct infrared spectroscopy, and scanning electron microscopy—to characterize the particles. According to the paper, “we show the universal presence of microplastics in human bile,” identifying six polymer types dominated by polyethylene terephthalate and polyethylene, with most particles measuring 20–50 μm. Patients with gallstones carried substantially higher microplastic burdens, raising questions about whether biliary stasis or altered bile composition may influence microplastic retention.
This schematic summarizes the study workflow and main findings. Human exposure to microplastics may occur through multiple routes, including industrial pollution, airborne exposure, food packaging, drinking-related plastics, and consumer products. Bile samples collected from individuals with and without gallstones were analyzed using Py-GC/MS, LDIR, and SEM, which confirmed the presence, polymer composition, particle size, and morphology of microplastics in human bile. Mechanistic experiments further showed that nanoplastic exposure induced cholangiocyte senescence by triggering mitochondrial dysfunction, including increased mitochondrial reactive oxygen species, enhanced Drp1-mediated fission, reduced mitochondrial membrane potential, and decreased ATP production, while melatonin partially alleviated these toxic effects. [Environmental Science and Ecotechnology]
To probe biological effects, the researchers exposed cultured human cholangiocytes to low-dose polystyrene nanoplastics for seven days, simulating chronic exposure. The cells exhibited mitochondrial dysfunction, elevated reactive oxygen species, reduced ATP, Drp1‑mediated mitochondrial fission, and G1 cell‑cycle arrest—hallmarks of senescence. As the authors wrote, chronic exposure “induces mitochondrial dysfunction-associated senescence in cholangiocytes,” suggesting a mechanistic link between environmental microplastics and biliary aging.
One of the most intriguing findings is that melatonin, a widely used antioxidant, partially reversed the mitochondrial and inflammatory damage. While far from a therapeutic recommendation, the result hints at a potential intervention point and gives the study translational relevance.
The work reframes the biliary system as something far more active than a simple transit channel. The data indicate that bile can serve as a reservoir for microplastics and that prolonged exposure may age cholangiocytes by driving mitochondrial dysfunction. The partial rescue with melatonin adds a mechanistic foothold for future intervention, even as the authors caution that broader human studies are essential.
For biotech, the implications are broad. The work highlights bile as a clinically accessible matrix for exposure assessment, opening the door to new diagnostics for environmental toxicology. The mitochondrial stress signature aligns with pathways already being targeted by companies developing senolytics, mitoprotective agents, and anti‑inflammatory therapeutics. The authors wrote that the research provides “a mechanistic foundation for assessing the health risks of plastic pollution and developing therapeutic interventions for environmentally driven biliary disorders.”
“It took me years to find out that what I was dealing with was OCD!”
This is a phrase all too often repeated by people living with obsessive compulsive disorder. Currently, individuals live with OCD for an average of 7 years (Dell’Osso et al, 2019) before they even receive a diagnosis, all while symptoms may intensify and daily life often becomes increasingly constrained.
Clinicians, researchers, and advocates have long raised this concern. What has been missing is clear data behind how many people with OCD in the U.S. are missed in clinical settings or are not receiving the most effective treatment.
When the International OCD Foundation undertook this analysis, the scale of the problem became unmistakable. Millions of people in America are currently struggling with OCD without the most effective treatment.
Well established prevalence rates for OCD indicate that nearly 10 million people in America — roughly 3% (Ruscio et al, 2010; Stein et al,2025; Ringeisen et al, 2025) — will have OCD at some point in their lives. Yet our findings suggest that 75% of them are never even identified, and up to 95% aren’t receiving the most effective treatment for the disorder.
In our analysis, we discovered significant systemic breakdowns at several key points of a patient’s journey: screening, diagnosis, referral, and treatment.
Screening and Diagnosis: Receiving a clinical diagnosis is an important step toward recovery as it promotes understanding and opens paths to effective treatment. Yet our findings suggest that this crucial initial step is missing for many millions of people. Of the 10.4 million patient records reviewed in our analysis, only 0.51% received a formal OCD diagnosis, far below the 3% expected prevalence rate.
Referral to appropriate care: After a diagnosis is obtained, a handoff to appropriate care is needed to keep the patient from falling out of the treatment pathway. Here, too, we found an alarming gap within our sample: more than 72% of patients identified as having OCD did not receive a referral for cognitive-behavioral therapy (CBT), the most effective treatment for OCD.
Effective Treatment: Decades of research has established Exposure and Response Prevention (ERP) therapy, a specific form of CBT, as the most effective, first-line therapy for OCD. Yet, an astounding 95-98% of people with OCD had not received ERP treatment. Even when people seek help — and even when they are diagnosed — the vast majority never reach the treatment most likely to help them recover.
What We Can Do About It
The breakdowns seen in each step of the care pathway reinforce the focus of IOCDF’s Vision 2030, our five-year strategy to address the systemic barriers that keep effective OCD treatment out of reach.
While the findings are stark, they illuminate many opportunities for change:
Identify symptoms earlier by implementing routine OCD screening in primary healthcare and mental health settings.
Support clinicians in better understanding and treating OCD by expanding training in assessment, diagnosis, and evidence-based treatment modalities.
Help people receive care that works by strengthening adherence to existing professional treatment guidelines.
Increase the number of people with OCD who receive effective treatment by supporting affordable access to ERP and other evidence-based therapies.
Let people know they’re not alone by raising accurate public awareness of what OCD really is — and that it is treatable.
Vision 2030 outlines how the IOCDF is committing its resources, partnerships, and expertise toward advancing these priorities — by increasing awareness and community, expanding access to effective treatment, and advancing research. Together, these efforts are designed to work in concert, improving clinical training, implementing screening for early identification, strengthening pathways from diagnosis to care, and increasing the likelihood that people receive evidence-based treatment.
At the same time, the scale of the problem revealed in this report makes clear that progress depends on collective action across the field. Clinicians, health systems, educators, researchers, policymakers, advocates, and people with lived experience all have a role to play. Together, these efforts can help ensure that people with OCD reach effective treatment sooner, reducing years of unnecessary confusion and distress.
How You Can Help
Join us in building better access to effective treatment for people with OCD:
Share America’s OCD Care Crisis and other IOCDF resources with your clinicians and healthcare professionals.
Donate to the IOCDF to support training programs, advance research, and raise awareness of OCD and related disorders.
The current state of treatment for OCD in the U.S. is sobering, but it is not the end of the story. OCD is treatable, recovery is possible, and change can happen as awareness grows and access expands. With continued effort, the gap between how many are struggling and how many receive effective care can begin to close. A brighter future is possible — and we can build it together.
References
Dell’Osso, B., Benatti, B., Grancini, B., Vismara, M., De Carlo, V., Cirnigliaro, G., Albert, U., & Viganò, C. (2019). Investigating duration of illness and duration of untreated illness in obsessive compulsive disorder reveals patients remain at length pharmacologically untreated. International Journal of Psychiatry in Clinical Practice, 23(4), 311–313. https://doi.org/10.1080/13651501.2019.1621348
Ruscio, A. M., Stein, D. J., Chiu, W. T., & Kessler, R. C. (2010). The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Molecular Psychiatry, 15(1), 53-63. https://doi.org/10.1038/mp.2008.94
Stein, D. J., Ruscio, A. M., Altwaijri, Y., Chiu, W. T., Sampson, N. A., Aguilar-Gaxiola, S., Al-Hamzawi, A., Alonso, J., Chardoul, S., Gureje, O., Hu, C., Karam, E. G., McGrath, J. J., Navarro-Mateu, F., Scott, K. M., Stagnaro, J. C., Torres, Y., Vladescu, C., Wciórka, J., Xavier, M., … Kessler, R. C. (2025). Obsessive-compulsive disorder in the World Mental Health surveys. Research Square, rs.3.rs-6090427. https://doi.org/10.21203/rs.3.rs-6090427/v1
Ringeisen, H., Edlund, M., Guyer, H., Dever, J., Carpenter, L., Olfson, M., First, M., Geiger, P., Liao, D., Peytchev, A., Carr, C., Chwastiak, L., Dixon, L. B., Monroe-Devita, M., Scott Stroup, T., Swanson, J., Swartz, M., Gibbons, R., Stambaugh, L., Bareis, N., … Mental Health and Substance Use Disorders Prevalence Study Consortium (2025). Prevalence of past-year mental and substance use disorders, 2021-2022. Psychiatric Services (Washington, D.C.), 76(8), 720–728. https://doi.org/10.1176/appi.ps.20240329
IOCDF Training & Resources for Clinicians
When clinicians have easier access to best practices in OCD diagnosis and treatment, more people can receive effective care. The IOCDF’s Training Institute offers evidence-based programs for clinicians at every stage of practice, including:
A robust, on-demand webinar catalog (CE-eligible!) covering fundamentals, modalities, related disorders, and comorbidities. The catalog includes access to the free webinar, OCD Basics.
IOCDF’s Training Institute offers intensive workshops and events, consultation groups, and more for clinicians of every level.
Professional Members at the IOCDF join a nationwide network of committed professionals, are eligible for listing on our Resource Directory, and have access to special pricing for Training Institute offerings.
Background: Periodontitis is a chronic gum disease affecting approximately 42% of adults aged 30 years and older in the United States. Training dental students to accurately diagnose and manage periodontitis is a critical component of dental education and clinical care. Recent advances in large language models offer new opportunities to support both domains, yet their performance in periodontal diagnosis remains largely unexplored, particularly for newer models such as GPT-5. Objective: This study conducted an exploratory evaluation of GPT-5’s ability to stage and grade periodontitis. Methods: A total of 25 publicly available clinical cases explicitly reporting periodontitis stage and grade were identified through Google and PubMed searches. Each case description was entered into GPT-5 using a zero-shot prompting approach to assess guideline-based reasoning without exemplar conditioning. The model’s predictions were compared with the published reference diagnoses. Performance was measured using accuracy, 95% CI, unweighted Cohen κ, and weighted Cohen κ. Results: Across these cases, GPT-5 showed marked class-dependent performance and a tendency to overestimate disease severity. Grading performance was notably imbalanced, with high recall for grade C but substantially lower discrimination for grade B. GPT-5 achieved a staging accuracy of 68% (95% CI 48.4%-82.8%) and a grading accuracy of 77.3% (95% CI 56.6%-89.9%), with corresponding Cohen κ values of 0.454 (95% CI 11.0%-75.6%) and 0.179 (95% CI −15.8% to 63.8%), respectively. While staging performance showed fair agreement beyond chance, the low κ for grading indicates poor agreement and limited reliability in distinguishing periodontal disease severity. Conclusions: These findings suggest that although GPT-5 demonstrates potential for guideline-based periodontitis staging and grading, its current diagnostic performance, particularly for periodontitis grading, limits its use in clinical assessment and educational training. Meaningful application in periodontal diagnosis and training will require substantial improvements in reliability and rigorous validation in larger, more diverse, and prospectively collected datasets.
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<strong>Background:</strong> In recent years, large language models (LLMs) have undergone swift cycles of refinement and iteration. However, in the realm of clinical medicine, different LLMs’ capability of logical reasoning and disease diagnosis needs further investigation. <strong>Objective:</strong> The aim of our study was to evaluate the performance of 4 different LLMs in the National Health Professional and Technical Qualification Examination in China. <strong>Methods:</strong> A total of 398 multiple-choice questions of 5 different question types were integrated within the examination with respect to the diagnosis or care of cases. These questions were categorized into different cardiology subspecialties and different clinical disciplines. DeepSeek V3 and R1 were accessed through an application programming interface, while ChatGPT 4o and o1 were queried via its public chat-based interface. We offered the same prompts instructing LLMs to assume the role of a physician and provide answers with explanations at the beginning of each conversation. We assessed different LLMs’ performance by the accuracy in the responses to the multiple-choice questions. For the first 3 examination sections, McNemar test was used to compare the accuracy among the models, with post hoc pairwise comparisons performed using partitions of chi-square method and Bonferroni correction (significance set at <i>P</i><.008). For the fourth section involving partially credit scoring, one-way ANOVA was performed to compare the mean scores among the models, with statistical significance set at <i>P</i><.05. <strong>Results:</strong> Both DeepSeek V3 and R1 showed superior performance in the first 3 sections of the Chinese National Health Professional and Technical Qualification Examination, achieving an overall performance of 93% and 93.6%, respectively. ChatGPT 4o and o1 achieved accuracies of 73.3% and 69%, respectively (all <i>P</i><.001 compared with DeepSeek V3). For the fourth section, the performance of all 4 LLMs markedly declined compared to their results in the preceding sections. Particularly, in the section of gastroenterology and hematology, DeepSeek V3 achieved the highest accuracy, while R1 ranked first in cardiology and neurology. ChatGPT o1 achieved the highest accuracy in the topic of coronary artery disease, with no statistical significance. <strong>Conclusions:</strong> DeepSeek V3 and R1 showed remarkable potential in facilitating clinical decision-making in the Chinese professional examination, with both outperforming ChatGPT 4o and o1. Nonetheless, future research should continue evaluating their economic efficiency and susceptibility to hallucination.
Large language models are rapidly becoming embedded in everyday life through artificial intelligence (AI) chatbots that people use for practical assistance and companionship, as well as for support with mental health and emotional wellbeing. Alongside clear benefits, clinicians and public reports increasingly describe a minority of users whose interactions seem to drift over days or weeks toward strongly questionable convictions, delusions or suicidal crises. Importantly, clinically meaningful deterioration can occur even without overtly unsafe text outputs, via more insidious processes such as compulsive use and sleep disruption, as well as withdrawal from human contact and progressive narrowing of attention around the chatbot relationship. In this Viewpoint, we argue that risk often arises not at a single tipping point but through trajectory effects that accumulate across extended dialogue, and that prevailing safety evaluation approaches are misaligned with this reality because they primarily score risk at discrete conversational endpoints often reached through scripted dialogues lasting just a single turn or several turns. Mental health benchmarks and safety suites (including clinician-informed efforts) have advanced the field by testing refusal behaviour, toxicity, and adversarial prompting, but they often treat the last message as the unit of analysis and therefore miss when risk-relevant relational cues, signs of validation, contradiction handling, and shifts in certainty first emerge and how they compound. We propose that mental health safety assessment should shift from endpoints to trajectories by 1) treating the whole dialogue, not just the end result, as the focus of evaluation; 2) reporting turn-by-turn dynamics such as delusion confirmation and harm enablement, as well as timing and persistence of safety interventions; and 3) calibrating short multi-turn tests against longer, clinically realistic interaction sequences that can reveal context-length effects and drift. We further argue that transcript-only evaluation is insufficient in mental health contexts. Similar language can reflect very different internal states, and the relationship between expressed psychopathology and real-world harm is non-linear. Safety research should therefore incorporate proximal human outcomes after interactions (e.g., shifts in certainty, openness to counterevidence, arousal, urge to continue, and subsequent sleep or behaviour) and build prospective clinical surveillance infrastructure that supports consented transcript donation and linkage to health outcomes. Together, these steps would enable benchmarks that are clinically relevant and better aligned with the kinds of harms now being observed in real-world chatbot use.
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Although immunoglobulin G (IgG) normally protects the body against pathogens, it can become problematic in many autoimmune diseases like lupus, rheumatoid arthritis, Graves’ disease, myasthenia gravis, and Sjögren’s disease.
“In these conditions, the immune system is creating defective IgGs—called autoantibodies—that are no longer fighting infections,” explained Eric Venker, MD, PharmD, CEO of Immunovant. “Instead, they are attacking a part of your normal functioning body and causing dysfunction.”
Leonard L. Dragone, MD, PhD Disease Area Leader Johnson & Johnson Innovative Medicine.
Historically, autoimmune conditions have been challenging to treat because therapies like steroids rely on broad immune suppression, noted Leonard L. Dragone, MD, PhD, disease area leader of autoantibody and rheumatology at Johnson & Johnson Innovative Medicine. These non-specific approaches are often inconsistently effective and lead to adverse side effects.
“For many autoimmune diseases, there is a need for more targeted strategies that address disease-causing autoantibodies directly, rather than broadly suppressing the immune system,” emphasized Dragone. Beginning in 1998, the U.S. Food and Drug Administration (FDA) approved infliximab, a tumor necrosis factor (TNF)-α inhibitor, for the treatment of Crohn’s disease. This marked the first approval of a monoclonal antibody for the treatment of a chronic condition. Since then, targeted therapies for autoimmune diseases have expanded to address cytokine signaling pathways (TNF-α, IL-6, IL-17, IL-23), Janus kinase (JAK–STAT) signaling, and immune cell surface markers (CD20).
Another such targeted strategy involves an emerging drug class called FcRn blockers, which are now showing considerable promise in the treatment of certain autoimmune diseases.
FcRn blockers, which typically consist of monoclonal antibodies or antibody fragments, work by blocking the function of a protein receptor called FcRn (neonatal Fc receptor). This prevents IgG recycling, thereby reducing IgG levels in the body.
FcRn maintains levels of IgG in circulation by preventing IgG degradation in the lysosomes of cells. However, FcRn drugs block this pathway.
Venker compares FcRn inhibitors to cholesterol-lowering drugs such as statins. “LDL is the disease-causing agent that healthcare providers target to prevent many cardiovascular diseases. Likewise, in the case of FcRn blockade, we are aiming to lower IgG. We believe that deeper IgG reduction may provide improved results.”
As of early 2026, the FDA has approved three FcRn inhibitors for the treatment of myasthenia gravis, a chronic autoimmune disorder affecting up to 100,000 people in the U.S. Efgartigimod (approved in 2021), rozanolixizumab-noli (approved in 2023), and nipocalimab-aahu (approved in 2025) all work by reducing pathogenic IgGs associated with the disease.
Myasthenia gravis results from harmful antibodies (anti-AChR or anti-MuSK) produced by the immune system that interfere with signaling in the neuromuscular junction.
“With FcRn blockers, it is exciting to know that there is now a targeted mechanism for patients around the world with autoimmune diseases caused by an IgG autoantibody,” said Venker.
Tackling Graves’ disease
In Graves’ disease, an IgG autoantibody called thyrotropin receptor antibody (TRAb), which targets the thyroid-stimulating hormone (TSH) receptor of the thyroid, is produced. The condition, which is the most common cause of hyperthyroidism, causes elevated heart rate, shakiness, irritability, muscle weakness, and weight loss.
“TRAb is an IgG antibody, but it is a badly behaving one that is basically hijacking the thyroid system,” noted Venker. “It doesn’t serve any purpose that is normal at all.”
Mark A. Lupo, MD Founder and Medical Director Thyroid & Endocrine Center of Florida
Unfortunately, the toolkit for treating Graves’ disease hasn’t changed much since 1950, when the FDA approved the drug methimazole, said Mark A. Lupo, MD, founder and medical director of the Thyroid & Endocrine Center of Florida.
Methimazole is an anti-thyroid drug that slows down the production of thyroid hormones. Although Graves’ patients benefit from anti-thyroid drugs, Lupo estimates a 50% relapse rate within two years of discontinuing these drugs.
Other options for treating Graves’ disease include surgical removal of the thyroid or the use of radioactive iodine to induce destruction of the thyroid gland. However, these approaches result in permanent hypothyroidism, and patients typically require lifelong thyroid hormone replacement after treatment.
Because TRAb is an IgG, FcRn drugs represent a potential autoimmune solution for Graves’ disease. Like all FcRn blockers, they may work by decreasing TRAb recycling and lowering TRAb levels.
Lupo highlights Immunovant’s recent proof-of-concept study of an FcRn inhibitor for Graves’ disease, the first such study for the condition. “Despite the small number of patients (around 25), the results from this study suggest a potential, durable remission six months off treatment,” said Lupo.
While study participants experienced an increase in total IgG levels following treatment, TRAb levels remained low over a six-month period. The thyroid also decreased in size. “To see TRAb levels down six months off the study drug caught the attention of the endocrine thyroid community,” noted Lupo.
“What was unexpected was that TRAb, the disease-causing antibody, stayed down for many months after stopping the investigational therapy,” added Venker.
“I think we are overdue for a new option in Graves’ disease that could help break some of these methimazole cycles and potentially address not the innocent thyroid gland but the underlying immune system issues,” concluded Lupo.
But are they safe?
Venker recalls that safety was an initial concern with FcRn inhibition. After all, these drugs work by reducing IgG, an essential part of the immune system. “Any time you are using an autoimmune drug that potentially suppresses your immune system, you have to think about going too far. Am I going to cause an infection or weaken the immune system?
“So far, this investigational drug has demonstrated a safety profile we expected, and appears positive,” noted Venker. “That makes sense mostly because FcRn blockade is pretty targeted.”
“Although there are no head-to-head comparative safety trials yet, most clinicians and principal investigators view FcRn blockers as relatively safe,” added Lupo. “There are FcRn blockers on the market, and they have demonstrated a good safety record in patients.” The most common side effect tends to involve injection site reactions with either intravenous or subcutaneous delivery.
Preventing fetal exposure
During pregnancy, maternal antibodies—called alloantibodies—can cross the placenta and attack the organs and tissues of the fetus, explained Dragone.
A distinguishing feature of Johnson & Johnson’s nipocalimab is its pH-independent binding to FcRn. This allows it to bind with high affinity in the placenta, a low-pH environment.
The drug is currently showing potential in the treatment of two alloimmune diseases of pregnancy: hemolytic disease of the fetus and newborn (HDFN) and fetal and neonatal alloimmune thrombocytopenia (FNAIT), said Dragone. These conditions can arise during alloimmunized pregnancies, when the pregnant person’s immune system forms alloantibodies against fetal red blood cells (HDFN) and/or fetal platelets (FNAIT). Importantly, published data on nipocalimab suggest minimal transfer of the drug to the fetus or infant. “Therapies like nipocalimab offer a blueprint for how precision medicine can expand to include pregnant people, a population that has historically been excluded from drug development,” noted Dragone. “Our approach with nipocalimab has the potential to change how we think about treating autoantibody-driven diseases in people of childbearing age.”
Nipocalimab (IMAAVY®) and other FcRn blockers bind to FcRn receptors and reduce levels of both normal and harmful IgG antibodies.
The FDA has granted a fast track designation to nipocalimab for both FNAIT and HDFN, and Phase III studies are underway to further investigate the drug in both diseases.
Expanding indications
“There are probably 20 trials out there for FcRn blockers, and many are likely to work,” noted Venker. “There are a ton of potential new indications under investigation, including rare diseases that have been ignored historically.”
He notes that Immunovant’s pipeline alone includes potential indications in endocrinology (Graves’ disease), rheumatology (rheumatoid arthritis, Sjögren’s disease, and cutaneous lupus erythematosus), and neurology (myasthenia gravis and chronic inflammatory demyelinating polyneuropathy).
Venker stresses that no FDA-approved solutions exist for Sjögren’s disease, which affects as many as four million Americans. The condition causes severe dry eyes and mouth, fatigue, and joint and muscle pain. Immunovant and Johnson & Johnson are conducting clinical trials to evaluate FcRn blockers for the disease.
Hani Houshyar, PhD Strategy Team Lead argenx
Meanwhile, argenx’s FcRn inhibitor efgartigimod has been used in 19,000 people worldwide for myasthenia gravis and other autoimmune conditions, said Hani Houshyar, PhD, FcRn asset strategy lead for argenx.
“However, we believe myasthenia gravis is just the beginning,” she said. As of 2026, the company has active clinical trials to test the drug’s effectiveness in additional autoimmune diseases with high unmet medical need, like myositis, Sjögren’s disease, ocular myasthenia gravis, systemic sclerosis, Graves’ disease, and autoimmune encephalitis.
UCB’s rozanolixizumab was the first FcRn blocker to be approved for the treatment of generalized myasthenia gravis in adults who are positive for anti-AChR or anti-MuSK antibodies, who together account for approximately 90% of cases, said Omar Sinno, MD, UCB’s U.S. medical strategy lead of rare disease. So far, the drug has been approved in the U.S., Canada, the EU, Australia, Switzerland, China, Turkey, and Korea.
Omar Sinno, MD Medical Strategy Lead, UCB
Rozanolixizumab is administered via a convenient subcutaneous infusion rather than intravenously. The company’s long-term studies demonstrate robust IgG reductions (up to 75%) with sustained benefit across multiple treatment cycles. UCB is also investigating rozanolixizumab as a potential treatment for a rare autoimmune condition called myelin oligodendrocyte glycoprotein antibody-associated disease.
Finally, Johnson & Johnson’s nipocalimab is in mid-to-late-stage studies for Sjögren’s disease, lupus, warm autoimmune hemolytic anemia, and chronic inflammatory demyelinating polyneuropathy.
Drugs in development
Viridian Therapeutics is currently investigating two FcRn inhibitors, VRDN-006 and VRDN-008, said Steve Mahoney, president and CEO. Both candidates are designed as subcutaneous products that can be conveniently self-administered by the patient.
Steve Mahoney President and CEO Viridian Therapeutics
VRDN-006 is an Fc fragment in Phase I trials, while VRDN-008 is made up of an Fc fragment and an albumin-binding domain designed to prolong IgG suppression. Mahoney notes that VRDN-008 showed a longer half-life and more sustained IgG reduction than efgartigimod in a high-dose, head-to-head study in non-human primates.
Clinical trial results of VRDN-008 in healthy volunteers are expected later in 2026. “What we believe differentiates VRDN-008 from other FcRn inhibitors is a longer half-life, which has the potential to support less frequent dosing for patients to enhance convenience,” said Mahoney.
Although three FcRn blockers are currently FDA-approved to treat myasthenia gravis in the U.S., Venker notes that Immunovant is continuing to investigate the condition with the company’s follow-on FcRn candidate, imeroprubart (IMVT-1402).
In Immunovant’s proof-of-concept study for Graves’ disease, TRAb stayed low even six months after the investigational treatment was discontinued. But how long will this effect last? “We don’t know that yet because our randomized trials with IMVT-1402 are ongoing,” Venker said. “However, Graves’ disease has given us the first hint that FcRn drugs may be able to put certain autoimmune conditions into permanent remission.”
Viridian’s VRDN-006 (top) is an Fc fragment, whereas VRDN-008 (bottom) is made up of an Fc fragment and an albumin-binding domain designed to prolong IgG suppression.
“A key question for autoimmune disease, the holy grail, so to speak, is whether we can reset the immune system so the person can function normally without medication for the rest of their lives,” he added.
Finally, argenx is developing ARGX-213, a next-generation FcRn inhibitor engineered to extend half-life and sustain IgG reduction.
“Looking ahead, FcRn inhibition represents an increasingly important approach across IgG-driven disease,” noted Sinno. “By selectively reducing pathogenic IgG, these agents enable more targeted autoimmune care. And as clinical experience with FcRn inhibition grows, treatment paradigms may shift toward earlier intervention.”
Tiffany Yesavage, PhD is a freelance writer from Denver, Colorado.
Since the first in vitro fertilization (IVF) baby was born in 1978, the options for couples or individuals struggling with infertility have improved exponentially. However, the core methods that make up this process are still fairly crude and associated with significant discomfort and side effects. This is something that reproductive endocrinologist Marie-Christine Maurel, PhD, chief scientific officer (CSO) and founder of Igyxos Biotherapeutics, is hoping to improve with the company’s first‑in‑class antibody treatment for infertility.
The antibody treatment—IGX12—amplifies the body’s own follicle-stimulating hormone (FSH) signal in both women and men, potentially improving production of both sperm and eggs with fewer injections than IVF and more physiological control.
Maurel has a doctorate in reproductive physiology from Pierre & Marie Curie University in Paris and worked as a post-doctoral fellow at the Pasteur Institute in Paris. The idea for the infertility treatment, which achieved promising Phase I results at the end of last year, originated from work at Maurel’s first biotech firm ReproPharm, which she co-founded in 2009 after winning a French “national competition for the creation of innovative companies.”
Maurel previously worked at the National Institute of Agronomic Research (INRA) near Paris for more than 25 years. Her group studied how gonadotropins affect fertility in animals and developed monoclonal antibodies that impact the activity of these reproductive hormones. ReproPharm initially used this research to improve fertility in farm animals, but when the team realized the same ideas could be applied to human infertility, the initial company was split into ReproPharm Vet and Igyxos in 2017 to focus on animal and human fertility problems, respectively. Alongside serving as CSO at Igyxos, Maurel remains president and CEO of ReproPharm Vet.
Maurel discussed her inspirations, research, and motivations for founding both companies with Inside Precision Medicine’s senior editor, Helen Albert, and outlined why Igyxos’s antibody could be so important if it achieves market authorization.
Q: What inspired you to become a scientist?
Marie-Christine Maurel, PhD
Maurel: When I was younger, I was passionate about science, and biology in particular. In my teens, I hesitated between choosing to study medicine or biological research. Finally, I chose biological research, but remained very interested in biomedicine. Currently, I mix both topics because we are developing a new medicine to treat infertility problems in humans, so it’s a mix of research and medicine. I still enjoy scientific research, so I don’t regret my decision.
Q: You worked in academia for a long time before you decided to make the move into industry. What inspired you to do that?
Maurel: In nature, there are lots of things that occur. You just have to discover them and know how to ask the right questions to understand how they work. Penicillin is an extraordinary example. And here it’s the same thing. We were doing experiments with sheep and goats. When we discovered that the ewes or does that secreted potentiating antibodies were hyper prolific and had high numbers of offspring, we wondered why. Normally, antibodies block the activity of a hormone and never enhance it. But in this case, we discovered that these particular antibodies were able to potentiate the activity of reproductive hormones. It was a marvelous result because it meant [that] it was possible to avoid the use of hormone treatment in animals. When my team and I discovered the existence of these potentiating antibodies, I quickly assessed their potential for application in both human and animal health. I wanted to develop and translate the research. The fact that there are potentiating antibodies for FSH is extraordinary, because antibodies are normally always inhibitory. I wanted to develop a potentiating antibody so we could have much more effective treatments for infertility. I also won a national competition for the creation of innovative companies, which helped with founding ReproPharm. It was a wonderful adventure to create a new biotech with our innovation.
Q: What did you learn from the experience of founding ReproPharm?
Maurel: I learned a lot of things. It was a human experience. I met a lot of people in medicine and industry who were very important for the development of the company and myself as well. These people helped me to build and to progress the company. Building a good network was important for me when I went into industry. I would also advise this for young people who want to create a biotech company. Meeting good people helps enormously!
Q: What made you decide to split ReproPharm into the two spinout companies, ReproPharm Vet and Igyxos Biotherapeutics?
Maurel: My research group was based at INRA initially. It’s a French academic research center focused on animal reproduction. We started with an animal reproduction problem linked to breeding ovine and caprine species, but early on, we tried our innovation on human hormones because we thought it could be an excellent approach to treat infertility problems in women. We developed an antibody against human FSH to see if we could enhance the activity of human FSH and in animal species. We got some money to carry out the first experiments and had very good results. We then decided to develop this innovation in human health, but needed more funds to develop it further. All our existing investors told us that they were unwilling to take the risk of investing in a company developing both veterinary and human medicine. It was impossible for them because it was not separated, so we decided to split the first company into two independent companies in 2017.
Q: Did any of your experiences at ReproPharm help you to do things better at Igyxos?
Maurel: First, I can say that at Igyxos, from the experience with ReproPharm, I wanted to do as much research and development on IGX12 as possible using our own funds, and license the therapy as late as possible because that gives us more freedom to develop it as we want to. I think it is necessary to be independent as long as possible for this reason.
Also, during the founding and development of ReproPharm, we developed a lot of animal models, which are very useful now to develop IGX12 for treating human infertility, both in men and women. So it was a very strong basis for Igyxos. All these animal models we developed at ReproPharm were important for developing IGX12 and getting it to clinical trials.
Q: Can you tell me a bit more about what you’re trying to achieve at Igyxos?
Maurel: FSH is exactly the same hormone in men and women. It has different target cells, but the molecule is the same. So one potentiating antibody could act on FSH either in men or women. It’s exactly the same mechanism of action, so we can develop the first treatment in men with oligozoospermia, for example.
We also want to develop a new and innovative treatment for women with infertility, which could be more efficient than current treatments that are burdensome and costly. Now it’s necessary to repeat the same hormone treatment four or five times to have a baby with a 50% chance of success. We think that it will not be necessary to repeat our treatment because we have a lot of proof of concept in animals. We have shown we can get better gametogenesis with better quality of ovulation than other methods.
Q: You reported Phase I results in December 2025. Were you happy with the findings?
Maurel: Yes, it was totally successful. We got very nice results. No adverse events, and we have some first efficacy results, so we can start Phase II trials, but we need to raise money first.
The trial results have helped to interest investors, and we are now in contact with several funds. If the fundraising is successful, we hope to be able to start Phase II trials soon.
Q: You mentioned that IGX12, if approved, would be the first such treatment for men with common fertility issues like oligozoospermia. Why have more treatments not been developed for men before?
Maurel: The problem of male infertility was not considered for a long, long time, perhaps because of cultural issues. Now there is a huge problem with infertility in men because sperm counts are decreasing. Numbers decreased from around 100 million per mL to 50 million per mL between 1973 and 2018. So this treatment is very necessary!
Q: Do you think that if your treatment is successful, it could make IVF more accessible?
Maurel: Yes, I think that it would allow a reduction in both time and economic cost, because as I said previously, the treatment will be more efficient, so no need to repeat it. We developed the concept that the antibody could act on the endogenous FSH. So, using our approach, it would not be necessary for women to inject FSH, because the antibody is able to boost the woman’s own FSH. In the animal health domain, we use the antibody only. We never inject endogenous hormones, so it’s very clean. In humans we will also only inject the antibody. We never inject FSH. So it’s a single injection per month. If we succeed, it’s a very big market and a very nice treatment for a lot of people.
Q: Could IGX12 make fertility treatment more targeted for specific people or certain population groups?
Maurel: Yes, for example, men with oligozoospermia. That means the sperm count is too low for natural conception. If it’s a very low level, it’s not even possible to do IVF. So we will target this category of men. In women, we will target those who don’t have a good predicted result with IVF, for example, if they have a low follicular count. So we plan to target these two populations, which have few chances to succeed at having children with current treatments.
Q: What are your future plans for Igyxos and ReproPharm Vet?
Maurel: For Igyxos, the current priority is to raise funds to start Phase II clinical trials, both in men and women. For ReproPharm Vet, the objective is to conclude an ongoing collaboration with a big veterinary and pharma partner.
Helen Albert is senior editor at Inside Precision Medicine and a freelance science journalist. Prior to going freelance, she was editor-in-chief at Labiotech, an English-language, digital publication based in Berlin focusing on the European biotech industry. Before moving to Germany, she worked at a range of different science and health-focused publications in London. She was editor of The Biochemist magazine and blog, but also worked as a senior reporter at Springer Nature’s medwireNews for a number of years, as well as freelancing for various international publications. She has written for New Scientist, Chemistry World, Biodesigned, The BMJ, Forbes, Science Business, Cosmos magazine, and GEN. Helen has academic degrees in genetics and anthropology, and also spent some time early in her career working at the Sanger Institute in Cambridge before deciding to move into journalism.
In a new study published in Science titled, “Mitochondrial metabolism and signaling direct dendritic cell function in antitumor immunity,” researchers fromSt. Jude Children’s Research Hospital have uncovered a new metabolic mechanism for how tumors disable immune “gatekeeper” cells that initiate response in the presence of cancer. The results offer a new path to improve immunotherapy.
Dendritic cells alert and activate tumor-killing immune cells as a critical part of anticancer immune response. The authors found that tumors reduce dendritic cell function by minimizing mitochondrial fitness to prevent anticancer immune response. Correspondingly, boosting mitochondrial function in dendritic cells enhances antitumor immune activity and strengthens the efficacy of existing immunotherapies.
Within the nutrient-sparse tumor microenvironment, dendritic cells progressively lose mitochondrial activity, which drives cell dysfunction and weakens immune defenses against cancer. When dendritic cells with high mitochondrial activity were introduced into tumors in preclinical mouse models, results showed that immunogenic activity was restored while improving tumor control.
“We found that tumors reprogram mitochondrial metabolism in dendritic cells, reducing their ability to activate the immune system against cancer,” said Hongbo Chi, PhD, St. Jude Department of Immunology chair and corresponding author of the study. “By enhancing mitochondrial function, we could restore dendritic cell activity and rescue antitumor immunity.”
Immunotherapies for cancer, such as immune checkpoint blockade, have greatly improved care for many malignancies, but have not been successful in all cancers. To determine whether these findings could improve immunotherapy effectiveness in tumor-bearing mice, the authors evaluated the administered dendritic cells with high mitochondrial activity in combination with immune checkpoint blockade.
“We saw the most pronounced therapeutic effect in mice treated with the combination of dendritic cells that had high mitochondrial activity and immune checkpoint blockade,” said co-first author Zhiyuan You, PhD, researcher at St. Jude Department of Immunology. “Those combinations synergistically slowed or stopped tumor growth and extended survival far more than either treatment alone.”
To test long-term effects, the researchers exposed combination therapy treated mice to a new tumor after a few months. New tumor growth stopped for these mice, indicating durable, long-term immune memory.
To better understand the relationship between mitochondrial function and dendritic cells, the researchers examined metabolic pathways affected by the tumor microenvironment. They identified a signaling axis composed of two proteins, OPA1 and NRF1, that regulate communication between mitochondria and the nucleus. Expression was greatly downregulated in dendritic cells during tumor progression and acted as a metabolic switch to shut down dendritic cell immunogenic activity.
“We’re seeing a direct regulation of dendritic cells by the tumor microenvironment,” said co-first author Jiyeon Kim, PhD, researcher at St. Jude Department of Immunology. “We have characterized how that results in mitochondrial reprogramming of dendritic cells to benefit cancer, giving us new opportunities to reverse the process.”
The study’s mechanistic insights enable new directions to rewire dendritic cell function and enhance cancer treatments.
“These findings reinforce the central role of dendritic cells in cancer immunity,” Chi said. “By exploring their mitochondrial function in the tumor microenvironment, we have provided a proof-of-principle of how we may be able to improve the next generation of immunotherapies.”
UCLA scientists have developed a simple and cost-effective blood test that, in early studies in more than 1,000 people, showed promise in detecting multiple cancers, various liver conditions, and organ abnormalities simultaneously.
The new method, called MethylScan, works by analyzing cell-free DNA (cfDNA), tiny fragments of genetic material released into the blood when cells die. Because cells from every organ shed DNA into the bloodstream, cfDNA carries molecular signals that reflect what is happening throughout the body.
The researchers say MethylScan could represent a powerful and more affordable approach to early disease detection and comprehensive health monitoring. “Early detection is crucial,” said research lead Jasmine Zhou, PhD, a professor of pathology and laboratory medicine and investigator at the UCLA Health Jonsson Comprehensive Cancer Center. “Survival rates are far higher when cancers are caught before they spread. If you detect cancer at stage one, outcomes are dramatically better than at stage four.” Zhou is senior author of the team’s published paper in PNAS, titled “Toward the simultaneous detection of multiple diseases with a highly cost-effective cell-free DNA methylome test.”
“When cells die, they do not simply vanish; they leave behind molecular traces, including cell-free DNA (cfDNA) in the blood stream,” the authors wrote. “cfDNA is a mixture of DNA fragments released from various organs, offering valuable insights into the health of these organs.” Zhou added, “Every day, 50 to 70 billion cells in our body die. They don’t just disappear, their DNA goes into the bloodstream. That means we already have information from all our organs circulating in the blood.”
The idea of using blood to detect cancer, sometimes called a liquid biopsy, isn’t new. Some tests already look for mutations in tumor DNA to screen for certain cancers. But those tests often focus on a limited number of genetic changes and can be expensive, in part because they require deep sequencing to detect faint tumor signals.
Instead of searching for mutations, the UCLA team examined DNA methylation, chemical tags attached to DNA that help regulate gene activity. Methylation patterns differ by tissue type and can change when cells become cancerous or diseased. “Unlike an individual’s genome, which remains largely stable across tissues and over time (except for rare somatic mutations), the DNA methylome is tissue-specific and dynamically changes with the tissue’s disease status,” the team continued.
“DNA methylation reflects the health status of a tissue,” said co-corresponding author Wenyuan Li, PhD, a professor of pathology and laboratory medicine at UCLA and co-corresponding author of the study. “It’s a very informative signal.”
The challenge is that most cell-free DNA in the bloodstream doesn’t come from tumors or injured organs. About 80% to 90% originates from normal blood cells. That creates background noise, making it difficult and costly to detect the relatively rare fragments that might signal early cancer. “A major challenge in using the cfDNA methylome for disease detection is the high cost of sequencing,” the team stated. “In healthy individuals, about 85% of cfDNA originates from blood cells, creating substantial background noise that can obscure cfDNA from tumors or diseased organs.” And as the authors further pointed out, “Current cfDNA methylation assays primarily focus on single clinical indications by targeting specific genomic loci.”
For their newly reported research the team built on past work to develop a technique to remove much of the background DNA before sequencing. Using specialized enzymes, they selectively cut away unmethylated DNA fragments that largely come from blood cells. By designing a genome-wide hybridization panel, the captured DNA fragments are enriched for methylated DNA from solid organs, including those that are potentially diseased. “The MethylScan method is a targeted methylation assay that combines Methylation-Sensitive Restriction Enzymes (MSRE) digestion with a custom panel to enrich hypermethylated cfDNA from tissues beyond blood, enabling cost-effective detection of multiple diseases,” they wrote.
By removing the noise, the researchers say they can dramatically reduce the amount of sequencing needed, lowering costs while maintaining sensitivity. Achieving an effective sequencing depth of 300× per sample requires only 5 Gb of data, which would cost less than $20 if the price per gigabase is under $4.
To test the accuracy of MethylScan, the researchers analyzed blood samples from 1,061 people, including patients with liver, lung, ovarian and stomach cancers; individuals with liver diseases such as hepatitis B, hepatitis C, alcohol-related liver disease, and metabolic-associated liver disease; people with benign lung nodules; and healthy participants. Machine learning algorithms were then applied to analyze the complex methylation data.
For multi-cancer detection, the test achieved a high level of overall accuracy. At a specificity of 98%, meaning few false positives, it detected about 63% of cancers across all stages and roughly 55% of early-stage cancers. The test also performed well in liver cancer surveillance among high-risk individuals, including those with liver cirrhosis or HBV, detecting nearly 80% of cases at a specificity of just over 90%, meaning a less than 10% false positive rate.
Beyond simply detecting cancer, the methylation patterns helped identify where in the body a signal was coming from, known as the tissue of origin. “Being able to trace signals back to their source is important because a positive blood test needs to be followed by imaging or other diagnostic procedures directed at the right organ,” said Li.
MethylScan can work like a health radar for the body. By reading DNA signals in the blood, it can tell when specific organs, such as the liver or lungs, are under stress or damaged, even without knowing the disease in advance. The researchers also showed that the blood test could distinguish between different types of liver disease, including viral hepatitis and metabolic-associated liver disease. It correctly classified about 85% of patients, suggesting blood-based DNA testing could reduce the need for invasive liver biopsies.
Although larger prospective trials will be needed to confirm its performance in real-world screening, Zhou said the work represents an important step toward a single, affordable blood assay that can detect a broad spectrum of diseases earlier and more comprehensively than current methods allow.
“Because cfDNA in blood originates from multiple organs, and MethylScan captures a broad spectrum of robust hypermethylation markers, this assay has the potential to detect a variety of diseases, provided that appropriate training cohorts are available,” the investigators stated. “This versatile approach enables affordable, wide-ranging cfDNA tests that can identify various health conditions simultaneously, with the potential to transform early disease detection and health monitoring across diverse clinical settings.
Zhou added, “This study demonstrates that blood-based methylation profiling can deliver clinically meaningful information across multiple diseases. It’s an exciting advancement that brings us closer to realizing the dream of a single assay for universal disease detection.”
As a postdoctoral researcher at the University of Pennsylvania, Haijiao Liu, PhD, helped advance tumor-on-a-chip technology, a feat of bioengineering that mimics the microenvironment of malignant human tumors. Led by Dan Dongeun Huh, PhD, a Penn Engineering professor and trailblazer of organ-on-a-chip technology, Liu and his team explanted lung adenocarcinoma tumors onto the transparent chips to test their perfusion with chimeric antigen receptor (CAR) T cells. Their findings were published in October in Nature Biotechnology, with Liu as first author.
Now on paternity leave in Toronto, Liu spoke with Lindsey Leake about the implications of this work, the challenges inherent to tumor-on-a-chip studies, and his plans to launch a lab of his own this fall.
Q: Walk me through the creation of the tumor-on-a-chip. What went into its design?
Haijiao Liu: It’s essentially inspired by the need for alternative tumor models. This is speaking to the traditionally used animal tumor models and some existing in vitro tumor models, especially for the study of immunotherapies.
For example, when I started at Penn around 2018, Penn Medicine was pioneering this immunotherapy called CAR T-cell therapy, which is basically aiming to harness the patient’s own immune system, specifically the patient’s own T cells, to help fight the cancer. Penn Medicine was demonstrating huge clinical success using this CAR T therapy to treat blood cancers, such as leukemias and lymphomas. In a huge contrast to this, the solid cancer arena has seen a limited response from this new immunotherapy. So there’s this great need to study why this has not been successful, and that comes down to the consensus that the solid tumor has this really complex microenvironment.
In the category called tumor-on-a-chip, people try to control the cultural environment, the biochemical and biophysical environment of tumor cell cultures. We can use this for simple drug testing—see how the tumor growth will be affected or how effectively they can be killed. However, these existing tumor-on-chip or in vitro tumor models are still very simple. They don’t usually recreate or reproduce the complex structure of the human solid tumors that I described, like where they often include complex vessel networks.
I took the lead to address the need and the challenges of reproducing and then investigating, or probing, the dynamic interactions between those CAR T cells and human solid tumors entirely in vitro.
Q: How does the vascularization work on the chip?
Liu: It took several years to start, from the idea of building this more advanced tumor-on-a-chip technology toward proving it’s actually useful. I started by focusing on this one aspect, which is the CAR T-cell trafficking and their functions after they traffic to fight the tumors, and that will involve the recreation of the structural interface between the tumor and this complex vascular network that’s present in human tumors.
I was inspired by in vivo tumor transplantation, where traditionally, people take human tumors and then transplant them in a bulk, intact format into animal models. So my idea was, if we want to focus more on the human biology, if we want to engineer this entirely in vitro, how about we design a vascular bedding, like a miniature living model?
We basically took advantage of the self-assembly capability of human-sourced endothelial cells, combined with certain stromal fibroblasts, or stromal cells. With a bit of optimization, engineering, tweaking, then we can allow them to form capillary-like vascular networks in our engineered models.
Q: What are the advantages of recreating the tumor microenvironment in this way? That is, is the Petri dish becoming obsolete in cancer research?
Liu: The unique advantage of this way of engineering is to have a higher level of control over the structures of the tissue-tissue interface that we can build. For example, we can engineer different culture chambers. We can engineer different access windows with this model. That allows us to construct, step by step, the vascular bedding and then the tumor transplantation. Also, by forming these perfusable vessels—by the way, we can provide the infusion and flow of the CAR T cells, just like they are infused and flow in the patient—that gives us the leverage to reconstruct, probe, and then control these tissue functions in a highly precise manner.
Q: How did you and your colleagues at Penn explore CAR T-cell activity on the chip?
Liu: We first used different functional assays, like immunostaining and ELISA (enzyme-linked immunosorbent assay) assays, to characterize how the CAR T cells are doing and how they are interacting with the tumors in our engineered model. Then we disassembled this engineered tissue to extract all the cells for flow cytometry, to further characterize their functional phenotypes.
With the help of our collaborators and other people in the lab, I took advantage of this engineered model of vascular tumors interacting with CAR T cells for multi-omics analysis. For example, I was able to extract all the cells and send them for single-cell RNA seq[uencing]. We were able to look at the gene expressions of each individual cell from all the cell types that we included in this model. In this way, we have almost like a superpower to probe and read into how each cell—including the CAR Ts and tumors and the vessels—how they are responding and interacting with each other at the molecular gene levels. This is so powerful that it helped me to discover novel interactions between these parties and also new druggable targets.
The message is that through the development of this more advanced tumor-on-a-chip technology—combined with advanced multi-omics analytics and advanced computational analysis—we were able to provide this powerful in vitro technology to apply to accelerate the development of cell therapies, such as the CAR T immunotherapies for cancer, but also other complex diseases.
Q: What are the overall implications of this latest research?
Liu: With a growing understanding of human biology at the cellular and tissue levels, I think we’re seeing that our ability to engineer and design biological systems is also growing. More than ever, we have these advances in the ability to precisely construct, investigate, and then eventually control very complex tissue functions, and even organ functions. For example, our demonstrated tumor-on-a-chip technology is like presenting a miniature sandbox; we can literally see and predict the battlefield of CAR T therapy in cancer.
If we combine these advanced engineering technologies with emerging technologies in spatial multi-omics and the unprecedented productivity of the AI revolution, we will be able to accelerate the understanding of more complex human biology and extract more biological insights, and then apply that to accelerate the development of safer and more efficacious drugs and therapies, such as immunotherapies in cancer.
Q: What are the limitations of organ-on-chip technology that need to be overcome?
Liu: I think there are challenges on two fronts. The first limitation is the lack of complexity. We’re claiming that what we just published is a sufficiently complex system for us to deeply probe and understand the dynamics of CAR T tumor interactions. Still, if we’re speaking next level of translational power or potential, then we need to pursue a higher complexity that incorporates the missing but critical components from in vivo.
The other side of the coin is that if you make this engineered model more complex, you make it more challenging to reproduce or to scale up or to translate to other labs. But also, that points to an opportunity and growing room for translation, to standardize every single step, from the construction to the analysis of these engineered models, and to automate these processes as much as possible.
Q: What do you envision for your new lab?
Liu: I have a lot of things I want to do. I’m eager to establish my own team. The overarching and the unifying theme of the new lab will be to develop the next generation of in vitro complex tissue models, or I call it assembloid tissue models. Assembloid basically means there’s a stem cell-based, three-dimensional complex tissue model that intentionally incorporates different cell types, to emulate the critical tissue-tissue interactions that determine the tissue- and organ-level functions. I still need to make a big decision where the lab could be; it could be in Canada and it could also be in China.
Q: What impact might tumors-on-a-chip have on the future of precision medicine?
Liu: It’s attracting a lot of attention from biologists and clinicians who are heavily focused on using the traditional tissue models—animal models, for example, or the simple dish cultures—for their studies of interest. So the biggest impact I can foresee with our technology is that now it’s more mature. I can see it being gradually, and maybe quickly, adapted into more traditional biological labs, to help them dissect the complex biological questions they’re asking, or to accelerate the evaluation of the exciting new drugs or therapies they’re developing. Overall, I can see that accelerate this development pipeline of new drugs and therapies in precision medicine.
Lindsey Leake is an award-winning, independent health reporter based outside Washington, D.C. She spent 15 years as a staff journalist at outlets including Fortune, the USA TODAY Network and Sinclair Broadcast Group. She holds an MA in Science Writing from Johns Hopkins University, an MA in Journalism and Digital Storytelling from American University and a BA from Princeton University.
