Over the last decade, there has been unprecedented success and progress in immunotherapy for cancer treatment, so says Ira Mellman, PhD, the president of research at the Parker Institute for Cancer Immunotherapy during his opening keynote at the Frontiers in Cancer Immunotherapy Symposium hosted by The New York Academy of Sciences, held on June 23, 2026.
Through his talk, Mellman described the research and clinical seeds that were sown over the last two decades. He showed how these seeds have blossomed, and his expectations for which blossoms will bear fruit, with the right focus and pruning.
The last decade of cancer immunotherapy
Before considering therapeutic options, Mellman summarized the biological events required for stimulating an effective immune response in patients. He described the dual stages of T cell activation and T cell exhaustion. Most therapies have relied on interventions that activate T cells, but over time, these T cells become exhausted—they don’t die, but go into senescence.
The next logical step in therapeutic investigation was to explore methods to pull exhausted T cells from senescence back into an active state. While some new therapies are being tested, there is still significant work to be done and there have been many false starts.
Vaccine therapy has emerged to get ahead of the activation-exhaustion problem by developing primed and more efficient T cells.
“The sole purpose of vaccine therapy, as we think of it, is to generate more and better T cells by immunizing against presumptive tumor associated antigens or neo antigens and …having those cells feed into the cycle,” Mellman said. He explained that the idea behind using vaccines is akin to the goal of adaptive therapies, like CAR T, that increase the number of primed and functional T cells, but vaccines do it endogenously.
Broadening his scope further, Mellman spoke about cancers not just in terms of the direct interaction between cancer cells and T cells, but in the broader context of the body. “The tumor microenvironment (TME),” he said, “plays an immense role—both positive and negative—with respect to allowing T cells to do their jobs in the case of anti-tumor immunity.” Consideration of the interactions between cancer and the TME present both opportunities and challenges to developing therapies.
Current progress
“We’ve had unprecedented success both clinically and commercially” within the last 15 years for a variety of cancer therapies that have come from the research stage to FDA approval in a relatively short time. Mellman pointed out that these therapies not only have been created quickly, are effective across a variety of diseases, are well tolerated, and improve survival of patients.
“All of this activity together has really changed the standard of care in a wide variety of cancer types,” he stressed. “That this has happened over a 15-year period is truly extraordinary.”
Why is a renaissance needed?
With this progress, Mellman returned to his original thesis that the field of cancer immunotherapy is on the precipice of big change.
He asked, “With this success—including clinical and financial—why do we need a renaissance in this area?” He answered his own question stating, that “We are the victims of our own success.”
He described challenges and setbacks stemming from the early progress. He described that identifying new checkpoint targets have not been successful, TIL research is somewhat successful, but outcomes are inconsistent, solid tumors post problems for therapies like CAR T, and cancer vaccines efficacy is unconfirmed except in their use as a post-operative adjuvant.
Reflecting on the history and progress, Mellman presented his four top priorities in progressing cancer immunotherapy over the next ten years. First, focusing on the next generation of cell therapy, especially focusing on treating solid tumors. Second, he suggests moving past CARs to using neoantigen-driven targeting (including vaccines, synthetic neoAg, and TCR platforms). Third, prioritizing in vivo immune engineering to reduce costs and improve accessibility and scalability. Fourth, he stresses the need to focus on a holistic approach to cancer immunology, understanding and optimizing the TME cancer interactions, developing synthetic modulators and utilizing AI models guided by patient insights.
Current steps to the future
Mellman further explained that through his work over the last two decades, he’s learned many lessons. He pointed out that researchers and clinicians need to remember that there are many therapeutic opportunities derived from various approaches; he cautioned against forgetting that mice are not humans and vice versa, pointing out that what may work in one species may not in the other; he encouraged the use of new technologies, including integrating AI into analysis procedures; and finally he suggested that researchers build on clinical research not just laboratory work.
Focusing on his own work, Mellman described how his team integrated these lessons in studying the application of mRNA vaccines. He described a study comparing the outcomes of patients with pancreatic cancer given mRNA vaccines intravenously (IV) or with an intramuscular (IM) dose. They were surprised to find that patients receiving IV delivery responded to the vaccine, but the response was inconsistent at first glance. Through deeper investigation, they determined that non-responsive patients previously had a splenectomy in addition to the removal of their pancreatic tumor. They reasoned that the IV infusion in responsive patients impacted immune cells developing in the spleen. While this study helped explain part of the process, Mellman pointed out that the fundamental mechanisms by which vaccines can be functional as an adjuvant are still unclear and his team is currently working on addressing these questions.
“There is a wealth of new understanding that we can generate if we move to the clinic quickly but do so in a way that really still concentrates on the underlying basic science,” he concluded. He stressed the importance of following approaches with an established proof of concept and suggested that engineering will enable research and scaling up to positively impact many patients.
Tending to the blossoming research and application of cancer therapy will allow for patients to have the opportunity to have better therapies in the future. Though he said this early in his discussion, it seems appropriate to end with Mellman’s assertion that, “This is a remarkable field.”
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