Emerging Cellular Therapies at the Forefront of Cancer Immunotherapy

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ABSTRACT Support is requested for a Keystone Symposia conference entitled Emerging Cellular Therapies at the Forefront of Cancer Immunotherapy, organized by Drs. Francesco Marincola, Lisa Butterfield, David Stroncek and Marcela Maus. The conference will be held in Banff, Alberta, Canada from January 29-February 2, 2023. Cellular immunotherapy for the treatment of hematological malignancies and solid tumors is rapidly progressing. Progress depends upon the development of better products that match the challenges limiting effectiveness such as survival and engraftment, trafficking to cancer tissues, engagement with cancer cells, and resilience to immune-suppressive factors while at the same time de-risking toxicity. This can be only achieved following a holistic approach to achieve an optimal therapeutic index. Such estimation goes beyond the selection of antigenic targets based of differential expression between benign and neoplastic tissues as is intuitively done for small molecules, antibodies and other biologics where the engagement of the product with its target is dependent on stable chemistry and predicable pharmacokinetics. Cell therapies instead are affected by active rather than passive biodistribution, and context dependent potency. Thus, a broader range of factors need to be considered like product-dependent variability (fitness, unpredictable pharmacokinetics due non-specific trapping, sequestration and extravasation into normal tissues, and variable rates of in vivo expansion). Individual cancer immune biology may affect differential trafficking to benign compared to malignant tissues under different conditions of chemo-attraction, hampered engagement with cancer cells due to physical or functional barriers, immune suppression, and cellular dysfunction due to unfavorable metabolic conditions. This conference gathers expertise from all areas, to propose an integrated path forward to successful implementation of novel cellular therapeutics, particularly for solid tumors.