Category: Uncategorized

Posted on

StockWatch: Axiom CEO Explains Plans for Hong Kong IPO

Axiom Biosciences, a privately held developer of regenerative therapies and targeted biologics that rebranded last month from Cytonus Therapeutics, made headlines around the world when it announced plans to go public through an initial public offering (IPO), since companies that go public typically do so quietly, by filing registration statements with regulators and exchanges.

What made Axiom’s IPO plans even more newsworthy: the San Diego-area company (based in suburban Carlsbad, CA) said it intends to trade its first public shares on the Hong Kong Exchange (HKEX) rather than a U.S. market like Nasdaq, the leading market for biotech IPOs, or the New York Stock Exchange.

Why Hong Kong? Axiom says the special administrative region of China possesses deep biotechnology expertise, a strong appetite for clinical-stage innovation, and direct proximity to the Asian partners and capital advancing the company’s science.

“For us, Hong Kong is a very good fit for the stage of company that we’re in, and the timing is right,” Remo Moomiaie-Qajar, MD, Axiom’s founder, CEO, and chairman, told GEN. “Hong Kong has a very well-established investor base that really understands the time requirements and the capital needs for biopharma, but in particular, cell therapies. And ultimately, given the fact that we have been working in Asia with partnerships for several years, this landing spot for us in Hong Kong seemed to be the right choice in a broader strategy.”

Does that mean the United States is finished for biotech innovation?

“I would not state that at all,” he replied. “I think the United States is very much still a leader. It is also very central to our strategy, and the FDA is really core to all of our decisions moving forward into clinics. I just see that this is, and I speak only for us, part of a bigger global strategy which includes both Asia and the United States.”

“Ecosystem to thrive”

Remo Moomiaie-Qajar, MD, Axiom Biosciences founder, CEO, and chairman

However, Axiom has publicly offered other reasons for its move that convey a warmer biopharma climate in Hong Kong compared with the United States. In its announcement, the company said its Hong Kong IPO plans were “reflecting a broader shift in where the world’s most ambitious science finds the ecosystem to thrive.”

And speaking on CNBC, Moomiaie-Qajar raised a concern with the U.S. biopharma climate when it comes to financing: “Some of the most important science in the world is being built in the United States, but the way it gets funded hasn’t kept pace.”

He elaborated on that remark, telling GEN: “That speaks to a broad range of problems that we have in financing within this industry. In particular, I was referencing the private side.”

“The reality is, as you progress with your pipelines and you cross over the threshold of being a clinical stage company, and then you have clinical success, it requires a significant amount—more capital to get your assets to move forward, and hopefully, to a BLA [Biologics License Application],” Moomiaie-Qajar explained. “But the number of check writers diminishes at the same time. So, there is seemingly no shortage of capital within biopharma, but I do believe there’s a financing issue and an access issue.”

Hence Axiom’s exploration of whether this was the right time to go public—a question Axiom is answering in the affirmative: “Hong Kong, given our strategic fit, and relationships and proximity to our partners in Asia, was the right first decision in establishing our public identity as a company.”

Comeback mode

The IPO market has been in comeback mode most of this year, with 14 companies selling their first public shares on U.S. markets since January, and another five doing so overseas, in Asian markets that include the Tokyo Stock Exchange, South Korea’s tech-focused KOSDAQ, and the Hong Kong Exchange.

The biggest American biotech IPO—this year, and of all time—was an upsized offering that took place last month, when Parabilis Medicines (Nasdaq: PBLS)  raised an eye-popping $770.5 million in gross proceeds by selling some 38.5 million shares at $20 per share. Parabilis’ shares have risen 56% since then, to $31.28 at Friday’s closing bell.

The latest biotech IPO, also upsized, came on Thursday when Scribe Therapeutics (Nasdaq: SCTX), a developer of in vivo CRISPR gene-edited therapies, raised $128.7 million gross by selling 8.58 million shares at the high end of its price range at $15 per share. The shares jumped 44% on Friday, finishing the day at $21.65. Scribe also raised another $7.5 million gross by selling 500,000 shares at the IPO price to Sanofi (Euronext Paris: SAN) in a concurrent private placement.

But the best-performing U.S. biotech IPO is Veradermics (NYSE: MANE), a developer of treatments for dermatology and aesthetic conditions whose shares have catapulted more than six-fold, rocketing 545% since pricing its IPO at $17 per share on February 3, closing Friday at $109.66 per share. Earlier this month, Veradermics announced positive topline results from its open-label Phase II Study 207 trial (NCT06527365) assessing VDPHL01, an extended-release oral minoxidil formulation, in women with mild-to-moderate pattern hair loss.

Hong Kong’s largest biotech IPO so far this year is Suzhou Ribo Life Science (6938.HK), a developer of oligonucleotide treatments based on RNA interference and other technologies. Ribo raised more than HKD 1.8 billion ($229.5 million) by selling 31,610,400 shares at HKD 57.97 ($7.39) on January 9. Since then, however, Ribo’s stock price has dipped 7.5%, closing Thursday at HKD 53.60 ($6.83).

Also going public via HKEX this year were medtech companies such as Hangzhou Diagens Biotechnology (2526.HK), a developer of artificial intelligence (AI)-based medical imaging tools whose customers include specialized genomics research labs and cytogenetics labs, as well as hospital pathology departments. Diagens went public March 30, raising about $101 million by selling 7,999,200 shares at HKD 99.00 ($12.62)—a price that has since more than doubled, leaping 172% after closing Friday at HKD 269.00 ($34.30).

HKEX lists 84 biotech companies, compared with more than 600 for Nasdaq, according to their respective websites.

Staying in America

Over time, Axiom plans to pursue a secondary stock listing in the United States. Moomiaie-Qajar says Axiom will remain an American company: “We are a U.S.-based, U.S.-headquartered company that is going to be something that does not change.”

Axiom says it intends to be the first U.S. biotech company planning to go public in Hong Kong. That’s the path that was successfully trod by AI-based drug developer Insilico Medicine (3696.HK) when it went public in December, raising HKD 2.277 billion (about $292.3 million at the time; now worth $290.3 million) on the Hong Kong Exchange by selling 94,690,500 shares at HKD 24.05 ($3.08, now worth $3.06) each.

Insilico’s stock has nearly doubled, soaring 96% since then, closing Friday at HKD 47.06 ($6.00) thanks to several collaborations with biopharma giants and an upbeat revenue and profit forecast for the first half of 2026.

“From my perspective, it certainly seeded a little bit of certainty in my mind that this was a good decision, because they’ve done really well post-IPO,” Moomiaie-Qajar commented.

Insilico’s parent InSilico Medicine Cayman TopCo lists a registered office in the Cayman Islands, while Insilico’s website lists additional offices in Cambridge, MA (announced in 2024 as the company’s headquarters), New York, Montreal, Abu Dhabi, Hong Kong, Shanghai, and Taipei.

“Very high listing standards”

“One of the reasons you would list in Hong Kong is to openly compete with the companies in the ‘China Gym’ and also take advantage of the increased visibility and transparency with the very high listing standards,” Alex Zhavoronkov, PhD, Insilico’s chairman, executive director, CEO, and CBO, told GEN.

“Many companies want to list there. But the barriers for listing are very high even for the biotech track.”

A company planning to go public, he explained, needs not only an asset in Phase II studies, but a clear funding history from credible investors, several years’ worth of cash to operate, and a level of corporate stability that the exchange will assess.

“For very early biotech companies it may be much easier to list in the United States,” Zhavoronkov said. “In general, it is a positive trend because biotech must become more international and collaborate and compete internationally. Competing for capital is the advanced form of competition because finance usually runs biotech—you cannot discover and develop drugs without it. Companies and ideas in biotech should become more fluid internationally. Public listings make companies and ideas more competitive and transparent.”

Together with Seoul-based, privately held Medinno, Axiom has co-developed its lead regenerative therapy based on umbilical cord-derived, conditioned mesenchymal stem cells (MSCs) sourced from Wharton’s Jelly. The therapy is under study in two pipeline programs that aim to treat newborns with severe brain injury: AX-007 for intraventricular hemorrhage (IVH); and AX-008 for hypoxic-ischemic encephalopathy (HIE).

Positive Phase I results

Earlier this month, Axiom announced positive results from a Phase I dose-escalation study assessing the safety, tolerability, and preliminary efficacy of the regenerative therapy across a range of doses in nine newborns—five diagnosed with severe IVH, four with HIE—following direct administration into the central nervous system.

Across all doses studied, the MSC therapy achieved a 0% mortality rate at 12 months compared to the historical natural 46% mortality rate within the first year of life for infants with severe IVH. The therapy also showed a favorable safety profile, with no treatment-related serious adverse events seen.

“We’re now in discussions with the FDA to move those programs into the next stages, which would be a Phase IIb study,” Moomiaie-Qajar said. The FDA has granted AX-007 and AX-008 its Rare Pediatric Disease and Orphan Disease designations.

Axiom is also evaluating an expansion of its therapy development into adult ischemic stroke, which affects approximately 700,000 adults annually in the United States, and additional neurological indications.

“We feel very confident that given our clinical trial success in Phase I, the expansion of our valuable asset into three, four indications is going to be a good basis for us to launch our IPO, but then after the IPO really go further and deeper into our pipeline that we’ve been developing for eight years,” Moomiaie-Qajar said. “We have a lot now that we need to translate into clinics.”

Leaders and laggards

  • Immix Biopharma (Nasdaq: IMMX) shares tumbled 14% from $10.25 to $8.80 on July 20 following the arrest of Ronald L. Fischer, 70, who was one of Rhode Island’s Most Wanted fugitives—and who, under the alias of Richard Graydon, MD, PhD, served as the company’s CMO. Fischer was arrested by federal and Rhode Island authorities off the coast of New Jersey on a U.S. Marshals Service Unlawful Flight to Avoid Prosecution warrant, having been a fugitive since fleeing Rhode Island during a criminal trial in 2005, the U.S. Justice Department stated. Fischer was convicted in absentia of First-Degree Sexual Assault after failing to appear for trial and remained wanted for Failure to Appear, First Degree Sexual Assault, and Flight to Avoid Prosecution. Authorities also said Fischer was living on a 56-foot sailing vessel called The Silver Lining, which was registered under the Graydon name. As “Graydon,” Fischer was appointed Immix’s CMO in March, the company announced March 30 in a press release no longer posted on its website. “As of July 17, 2026, Richard Graydon has been terminated and is no longer with the company for reasons unrelated to his activities at the company,” Immix disclosed in a July 20 regulatory filing, adding: “Given his short tenure, management believes there is no material effect on the business.”
  • Novocure (NVCR) shares jumped 28% from $15.57 to $19.99 Thursday after the Swiss-based oncology drug/device developer developer of the Tumor Treating Fields (TTFields) cancer therapy reported second quarter adjusted earnings before interest, taxes, depreciation, and amortization (EBITDA) of $10.757 million, vs. an adjusted loss of $9.934 million a year earlier, on net revenue that rose nearly 16% year-over-year, to $183.584 million from $158.805 million. Novocure still finished Q2 in the red with a net loss of $15.658 million, improved from the $40.139 million net loss of the second quarter of 2025. Novocure credited its 18% global active patient growth across indications for the positive numbers; as of June 30, more than 280 active patients were on Optune Pax®, a wearable device designed to deliver its TTFields therapy for adults with locally advanced pancreatic cancer concomitant with gemcitabine and nab-paclitaxel. “The main takeaway is that the early U.S. adoption of Optune Pax is off to an encouraging start,” J.P. Morgan analyst Jessica Fye wrote in a research note. Novocure shares reached a 52-week high of $21.35 at the start of the trading day before sliding 12% to $17.65 on apparent profit-taking.

The post StockWatch: Axiom CEO Explains Plans for Hong Kong IPO appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on
<![CDATA[FDA clears Simtriyo, a first-in-class nonstimulant triple reuptake inhibitor for ADHD, offering new symptom and executive-function gains.]]>
Posted on

Direct Reconstruction of High-Fidelity Electrocardiogram Signals From Vector-Based PDF Files With Integrated Deep Learning for Multiparameter Estimation: Retrospective Methodological Study

Background: Electrocardiograms (ECGs) are commonly stored in PDF, particularly as vector-based files generated by ECG management systems. Previous studies have demonstrated that ECG signals can be extracted through PDF-to-Scalable Vector Graphics (SVG) conversion, highlighting the potential to reconstruct waveform signals from vector graphics. These reconstructed signals further enable the derivation and prediction of clinically relevant ECG parameters. Objective: This study aimed to develop an integrated framework for direct reconstruction of high-fidelity ECG signals from vector-based PDF files and for simultaneous estimation of multiple clinically relevant ECG parameters using deep learning. Methods: In this retrospective methodological study, 50,000 twelve-lead ECG PDFs generated by a MUSE system (2015‐2024) were analyzed. A direct PDF parsing pipeline was developed to extract vector path objects and reconstruct time-series signals without intermediate format conversion. Reconstruction accuracy was evaluated against the original system-exported signals. Two deep learning models, DualECGFormer and DualResNetECG, were developed to estimate 8 specific ECG parameters. The reference standards for these parameters—including ventricular rate; PR interval; QRS duration; QT interval; corrected QT interval (QTc); and the electrical axes of the P wave, QRS complex, and T wave—were derived from machine-generated values within the MUSE system database. Performance was compared with a rule-based approach (NeuroKit2). Results: The proposed method achieved high reconstruction fidelity, with mean absolute errors (MAEs) below 1×10 mV across all leads. Compared with an SVG-based workflow, the direct parsing approach reduced processing time by approximately 4.6-fold. For parameter estimation, deep learning models outperformed the rule-based method for most parameters. DualResNetECG achieved the best overall performance, with MAEs of 1.11 bpm for ventricular rate, 7.27 milliseconds for PR interval, 9.89 milliseconds for QRS duration, 11.87 milliseconds for QT, and 13.71 milliseconds for QTc. For electrical axis estimation, MAEs ranged from 8.0° to 16.31°. The model also demonstrated reliable detection of physiologically undefined parameters (PR interval and P-wave axis), achieving an area under the receiver operating characteristic curve of up to 0.978. Conclusions: This study presents an efficient and scalable framework for direct extraction of ECG signals from MUSE-generated vector-based PDFs and integrated multiparameter estimation using deep learning. The approach achieves high reconstruction accuracy and competitive predictive performance, supporting its potential utility for large-scale retrospective MUSE ECG analysis.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/52e7944094b005461b39ebeb183f7416" />

Posted on

Opinion: I led the FDA’s food safety and nutrition center. Here’s what people are missing about the cyclospora outbreak

I spent nearly a decade leading FDA’s Center for Food Safety and Applied Nutrition. That role convinced me that food safety and nutrition are interdependent in so many ways, and if we want to make our population healthier, we need to support both.

Over the past few weeks, record numbers of cases of cyclosporiasis have driven that message home broadly, including to consumers. FDA is currently investigating six cyclospora outbreaks, only one of which is currently linked to shredded iceberg lettuce.

Read the rest…

Posted on

Clinical Outcomes and Predictors of Improvement With Virtual Behavioral Health Care for Gambling Disorder: Retrospective Cohort Study

<strong>Background:</strong> Gambling disorder is associated with substantial psychiatric and functional burden, yet few individuals receive treatment. Limited real-world evidence exists evaluating outcomes of virtually delivered behavioral health care for gambling disorder, particularly among clinically complex patients. <strong>Objective:</strong> The purpose of this study was to evaluate gambling symptom severity outcomes among adults with gambling disorder receiving care from Birches Health. We aimed to (1) characterize the clinical profile of adults seeking treatment for gambling disorder; (2) quantify changes in gambling symptom severity over the initial 12 weeks of treatment and examine whether baseline clinical complexity, such as gambling symptom severity, depression severity, and psychiatric comorbidities, was associated with differences in gambling symptom severity improvement over time; and (3) estimate the timing and likelihood of achieving clinically meaningful improvement in gambling symptom severity. <strong>Methods:</strong> This retrospective cohort study included 1305 adults receiving virtual behavioral health treatment for gambling disorder through Birches Health between June 2024 and April 2026. Gambling symptom severity was assessed using the Gambling Symptom Assessment Scale (G-SAS) weekly. Linear mixed-effects models evaluated changes in gambling symptom severity over 12 weeks and associations with baseline clinical characteristics. Clinically meaningful improvement was defined as a reduction of 4 or more points in the G-SAS score. <strong>Results:</strong> Participants had a mean age of 41.5 (SD 13.1) years, 65.2% (851/1305) were male, and baseline gambling symptom severity was moderate (mean G-SAS score 20.5, SD 11.83). Over half (730/1305, 56%) of participants presented with at least one psychiatric comorbidity, most commonly anxiety disorder (351/1305, 26.9%) and depressive disorder (276/1305, 21.1%). Gambling symptom severity declined significantly over the first 12 weeks of treatment, with G-SAS scores decreasing by approximately 0.099 points per day (<i>P</i>&lt;.001), corresponding to an estimated 8.3-point reduction over 12 weeks. Higher baseline depressive symptom severity was associated with faster improvement in gambling symptoms (<i>P</i>=.01), whereas depressive disorder (<i>P</i>=.03) and attention-deficit/hyperactivity disorder (<i>P</i>=.008) diagnoses were associated with slower improvement trajectories. Among patients with routine follow-up assessments recorded during the initial 12 weeks of treatment (1071/1305, 82.1%), 71.7% (935/1305) achieved clinically meaningful improvement in gambling symptom severity, with a median time to improvement of 14 days. <strong>Conclusions:</strong> A clinically complex population of adults receiving care through a national virtual behavioral health care provider demonstrated rapid and clinically meaningful reductions in gambling symptom severity. These findings highlight the potential of specialized virtual care models to expand access to gambling treatment and support symptom improvement in routine care settings. Future research should evaluate longer-term recovery trajectories and identify factors associated with sustained improvement and ongoing engagement in care.
Posted on

FDA advisory panel narrowly rejects compounding of one peptide, backs two others

WASHINGTON — A Food and Drug Administration advisory panel recommended on Friday that compounding pharmacies be allowed to manufacture the peptides epitalon and semax, but narrowly voted to recommend against manufacturing emideltide. 

The votes, which followed the panel’s decision on Thursday to recommend allowing pharmacies to make four other peptides, bring health secretary Robert F. Kennedy Jr. one step closer to his mission of making these unapproved compounds more available for Americans. Peptides, which are short-chain amino acids, have become increasingly popular in the U.S., driven by endorsements from social media influencers.

Read the rest…

Posted on

Genetic Variants Linked to CAR T-Cell Efficacy and Safety

Scientists have identified variants in three genes that influence both the efficacy of CAR T-cell therapy and the likelihood of severe side effects. Published today in Science Immunology, these findings represent a first step toward adopting a precision medicine approach in an increasingly used form of cancer immunotherapy. 

CAR T-cell therapies have undeniably transformed the treatment of blood cancers, with a rapidly growing number of approvals over the past decade and progressively expanding toward solid tumors. While genetic variants associated with immune-related side effects have been identified for other forms of cancer immunotherapy, such as checkpoint inhibitors, the role of human genetics in CAR T-cell therapy has remained largely unexplored. However, this is particularly important given that most CAR T cells are manufactured from a patient’s own immune cells, meaning the therapy itself carries the patient’s unique genetic makeup. 

“Unlike traditional therapeutics that are essentially identical across all patients, CAR T cells are bespoke and harbor all of the ancestral genetic polymorphisms of their parental T cells,” write the study authors, led by Marcela V. Maus, MD, PhD, professor of medicine at Harvard Medical School and director of the Cellular Immunotherapy Program at Massachusetts General Hospital. 

Maus and colleagues analyzed data from 236 patients with aggressive lymphoma enrolled across two clinical trials, who had been treated with axicabtagene ciloleucel, a CAR T-cell therapy commercialized by Gilead under the name Yescarta. The analysis combined whole-genome sequencing with detailed biomarker and functional analysis to identify variants affecting the treatment’s efficacy and toxicity.

Among patients who developed treatment-induced toxicity, many carried variants of the STXBP2 gene. Follow-up experiments in human T cells showed that these variants increased the production of inflammatory cytokines and activated macrophages. Consistent with these findings, mutations in the STXBP2 gene have previously been linked to inflammatory bowel disease and a rare immune disease marked by excessive T cell activation. 

In contrast, variants in the ADMTSL3 gene were associated with protection against treatment-related toxicity, while variants in the PTPN22 gene were strongly linked to enhanced CAR T-cell expansion—a critical factor that determines treatment efficacy.  

“These findings demonstrate that germline genetics shape the safety and activity of engineered immune cell therapies, affecting future design and patient management,” write the scientists. Going forward, they plan to expand this research into larger patient cohorts and a wider range of CAR T-cell therapies to investigate how different genetic variants influence treatment efficacy and the risk of severe side effects across broader clinical settings. 

Beyond opening new avenues for precision medicine in CAR T-cell therapy, the researchers noted that these findings could also inform the development of off-the-shelf CAR T-cell therapies where donor-derived T cells are used instead of a patient’s own cells. This approach could enable a more precise selection of donor T cells optimized to maximize therapeutic benefit while minimizing toxicity risks. 

The post Genetic Variants Linked to CAR T-Cell Efficacy and Safety appeared first on Inside Precision Medicine.

Posted on

Molecular Atlas of Severe Preeclampsia Reveals New Therapeutic Targets

Researchers from University College London in England have created the most comprehensive molecular map to date of severe preeclampsia, uncovering distinct fetal and maternal drivers of the disease that could lead to more targeted therapies and earlier intervention.

The study, published in Science Advances, combined single-cell RNA sequencing with spatial transcriptomics across the entire fetal-maternal interface and found that severe preeclampsia is not solely a placental disorder. Instead, the disease involves coordinated dysfunction across multiple maternal and fetal tissues, with different molecular programs emerging in early- versus late-onset disease.

Preeclampsia affects 2% to 4% of pregnancies worldwide and remains a leading cause of maternal and fetal illness and death. Although it is traditionally viewed as a placental disease, the mechanisms responsible for widespread maternal inflammation and endothelial dysfunction have remained unclear.

To better define those mechanisms, investigators analyzed tissues from 20 pregnancies, including 10 women with severe preeclampsia and 10 gestational age-matched controls between 25 and 37 weeks of gestation. By matching pregnancies by gestational age rather than comparing preterm cases with healthy term pregnancies, the researchers were able to distinguish disease-related molecular changes from normal developmental differences.

The analysis revealed extensive placental abnormalities, including molecular signatures of hypoxia, angiogenic imbalance, fibrosis, and altered metabolism. The team also confirmed impaired invasion of fetal extravillous trophoblasts into the maternal uterus, a hallmark of preeclampsia that contributes to defective remodeling of maternal blood vessels.

Beyond the placenta, however, the study identified previously unrecognized maternal immune abnormalities extending into the myometrium and chorioamniotic membranes. These included widespread mitochondrial dysfunction, activation of type I interferon signaling, and altered macrophage responses, providing a potential explanation for the systemic inflammation and endothelial injury that characterize severe disease.

The findings point to several potential therapeutic targets. Leptin (LEP), which was strongly upregulated in placental cells throughout both early and late disease, may contribute to oxidative stress and vascular dysfunction. The researchers suggest that leptin antagonists, already under investigation for autoimmune diseases, warrant exploration as placental-targeted therapies.

The study also highlights type I interferon signaling as a promising target. Elevated interferon activity, detected in maternal immune cells and peripheral blood, could potentially serve as both a biomarker and a therapeutic target for anti-interferon or antioxidant treatments.

“IFN-I in peripheral blood promises better screening of patients that might benefit from anti-IFN or antioxidant therapeutics,” the authors concluded.

Perhaps most importantly, the molecular abnormalities were substantially more pronounced in early-onset disease, suggesting that intervention before clinical deterioration may offer the greatest benefit.

“Given the severity of molecular dysfunctions in early disease, compared to its late presentation, timely intervention during gestation is likely beneficial and could change the extremely poor prognosis of severe PE,” the authors wrote.

The post Molecular Atlas of Severe Preeclampsia Reveals New Therapeutic Targets appeared first on Inside Precision Medicine.

Posted on

Colorectal Cancer Targeted with Mass-Produced iPSC-Derived Allogeneic T Cells

Researchers at Kobe University have generated off-the-shelf, mass-producible induced pluripotent stem cell (iPSC)-derived gamma delta T cells (γδT cells) that in a small preclinical study suppressed tumor growth in mouse colorectal cancer (CRC) xenograft models. The team says their development could point to the potential for developing faster, cheaper cancer immunotherapy.

Research lead Takashi Aoi, PhD, and colleagues reported on the work in Stem Cell Reports, in a paper titled “Allogeneic iPSC-derived γδT cells demonstrate antitumor efficacy against patient-derived tissues,” commenting “Our current findings provide robust preclinical evidence supporting the efficacy of T cell therapy for CRC.”

“Various immunotherapies have been developed to treat malignant tumors, and autologous CAR T-cell therapy is clinically used for certain malignancies,” the authors wrote. However, CAR T-cell therapies demonstrate limited efficacy against solid tumors, and current techniques for modifying T cells extracted from the patient are expensive and time consuming. “… obstacles such as the time and cost required to initiate autologous treatment impede their widespread adoption.”

In the journal Stem Cell Reports, Kobe University stem cell researcher AOI Takashi and his team report that they created iPS cells from a subclass of T cells that can be used across patients and could reproducibly turn them back into T cells with an overall 80,000-fold multiplication and without using animal cells or extracts, and that the resulting T cells attack and shrink human patient-derived colorectal cancer tumors that were implanted into mice. [AOI Takashi]
In the journal Stem Cell Reports, Kobe University stem cell researcher Aoi Takashi and his team report that they created iPS cells from a subclass of T cells that can be used across patients and could reproducibly turn them back into T cells with an overall 80,000-fold multiplication and without using animal cells or extracts, and that the resulting T cells attack and shrink human patient-derived colorectal cancer tumors that were implanted into mice. [Aoi Takashi]

Consequently, the authors noted, there is growing interest in allogeneic, or off-the-shelf, cell therapy. Researchers have considered turning to a subclass of T cells called gamma-delta (γδ) T cells that don’t need to be tailored toward each individual patient but can be harvested from a donor and used in other people. “… the development of novel therapies for CRC, a highly heterogeneous cancer, remains a paramount challenge in global healthcare, and γδT cells are considered a promising candidate modality,” the authors stated. “γδT cells represent approximately 3–5% of peripheral blood lymphocytes and are capable of targeting various types of tumors in an MHC-unrestricted manner with a single type of γδT cell receptor.”

However, these cells are much fewer, making the harvesting approach infeasible, and they also cannot be directly multiplied well in the lab. Aoi stated, “Based on our experience with induced pluripotent stem cells, also called iPS cells, we thought that we could approach this issue by creating such easily storable and growable cells from these specific T cells, and then only turning them back into T cells when actually needed.” In their paper the authors added “We focused on γδT cells as a potential therapeutic modality for colorectal cancer (CRC).”

Through their reported study the investigators showed that they could create iPS cells from the subclass of T cells that can be used across patients and reproducibly turn them back into those T cells with an overall 80,000-fold multiplication. Importantly, they achieved this without relying on animal cells or extracts, which is a requirement for clinical applications. “To the best of our knowledge, this is the first study to report the successful induction of differentiation of γδT cells from iPS cells under feeder-free, serum-free conditions.”

Their study was also the first to show, on a small preclinical scale, that the resulting iPSC-derived γδT cells (iγδT cells) attack and shrink human patient-derived colorectal cancer tumors that were implanted into mice, with tumor weights in treated animals reduced by up to 88%, when compared with control mice.

“We demonstrated that these iγδTs exhibit cytotoxic activity against CRC and leukemia cell lines, as well as against patient-derived CRC organoids in vitro, while also exerting antitumor effects in vivo in xenograft models,” they noted. “Cancers from cell culture lines don’t have the same drug insensitivities as actual cancers and also don’t emulate the physical barriers that actual tumors have,” explained first author Ryoko Futai, PhD. “That’s why patient-derived organoids are highly significant for evaluating new cancer treatment approaches,” explained first author.

When they designed the study, the Kobe University team imagined that their approach would be used fighting metastasizing cancers. They also checked whether their T cells would find their targets not only when administered close to the tumor but when administered intravenously a week after the tumor was implanted. And indeed, even in this setting tumor weights decreased 43%, 82% and 92% in the three treated mice. Futai noted, “This suggests potential for future systemic therapy. We believe this achievement represents an important step toward the development of a new immunotherapy for solid tumors.”

The study was conducted at a small scale, with only three or four mice in each experiment and tumor models derived from only two different patients. This is especially important because colorectal cancer tumors are known for their high variability. “This study is a preclinical investigation demonstrating the potential using iPS cell-derived T cells and is not yet at a stage where it can be used on patients,” cautions Futai.

But by conducting further studies using these easily multipliable and very standardized cells, the Kobe University development may also be used to elucidate where the variability comes from and what steps to take to counter it. Aoi commented, “Furthermore, by combining this approach with cell modification techniques such as CAR therapy, we hope that this research will eventually lead to the development of new therapeutic possibilities for patients with solid tumors.” And in their paper the authors concluded, “Our findings will pave the way for the realization of off-the-shelf allogeneic γδT cell therapy.”

The post Colorectal Cancer Targeted with Mass-Produced iPSC-Derived Allogeneic T Cells appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on

The quest to keep organs alive outside the body

This week, I covered a fascinating effort to preserve organs outside the body. There’s a huge shortage of donor organs, and one of the main reasons is time—they survive only a matter of hours outside the body, even when they’re kept on ice.

Doctors dream of organ banks—stores of human organs that can be preserved for days, weeks, months, or even longer. That would allow them to run tests on organs, find the best matches for them, and transport the organs to those recipients.

In new research, one team has been able to supercool the kidneys of pigs—animals whose organs are of a similar size to human ones—and preserve them for days. The kidneys survived being stored at −4 °C (25 °F) and eventually reimplanted back into pigs. And that’s just the latest development in a field that is positively buzzing.

It has proved super difficult to freeze organs. Once ice forms in them, they’re done. The ice crystals create all kinds of damage and render the organs unusable. That hasn’t stopped many researchers from trying.

Some have focused on cryopreservation—rapid extreme cooling that essentially leaves cells in a glasslike state. This process is now routine for eggs, sperm, and embryos, which are cooled to −196 °C in less than two seconds and can be used even after decades in storage.

No one has managed to cryopreserve and thaw human organs for transplantation. But plenty of human bodies and brains have been stored at ultra-low temperatures in the hope that they might one day be rewarmed and brought back to life. (You can read more about why some people opt for cryonics here.)

In March, I wrote about Stephen L. Coles, a gerontologist who had opted to cryopreserve his own brain. After the scientist died in 2014, his body was taken to Alcor, a cryonics facility in Arizona. A team at the facility removed Coles’s head, perfused his brain with cryoprotective chemicals (which work like antifreeze), removed the brain from the skull, and cooled it to −146 °C.

When Coles’s friend Greg Fahy, a cryobiologist, studied pieces of his brain years later, he found that the brain cells, which had shrunk, “bounced back” once they were rewarmed. But that doesn’t mean the cells are alive, or that it might one day be possible to reanimate the brain. As Matthew Powell Palm of Texas A&M told me at the time: “There are so many ways those neurons could be toast.”

Powell Palm is working on other ways to preserve organs. It was he, along with his colleagues, who managed to store supercooled pig kidneys and successfully transplant them, in a study described as “a landmark achievement.” Those organs did better than kidneys stored on ice, he says.

His approach didn’t require cryoprotectants. But other teams are exploring potential chemical cocktails that might allow them to store organs at lower temperatures, potentially for longer periods of time. (More on this in The Checkup soon!)

Another way to prolong the lifespan of an organ is to use a machine that perfuses it with nutrients, mimicking what happens inside the body. Machine perfusion devices have become more commonly used over the last decade or so and are typically used to maintain livers and kidneys for up to about 24 hours.

Researchers are now adapting this protocol for a growing list of organs, even eyeballs—a recent feat that might enable whole-eye transplants. In March, I went to visit scientists in Valencia who had developed a perfusion system for uteruses. They had used their device—which they nicknamed “Mother”—to keep a human uterus alive for a day.

It’s an exciting time for organ preservation. Keep an eye out for more coverage from MIT Technology Review in the coming weeks.

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.