Addressing Patient to Patient Variability for Autologous CAR T Therapies

Chimeric Antigen Receptor (CAR) T cell therapy clinical trials have had unprecedented success in the endeavors to cure cancer patients, particularly those having hematological cancers. As researchers learn more about the ways to make CAR T cells more effective to kill tumor cells, equally important will be understanding the differences between T cells from healthy donors and cancer patients and how these differences could affect ex vivo expansion of T cells during CAR T production. This undoubtedly could be a crucial factor in treating solid tumors, where CAR T cells are needed in significantly higher numbers. As the evidence for significant differences between the patients and healthy donors is compelling, an adaptable and robust production process should be designed to allow manufacture of the required CAR T cells for all cancer patients. Improving the fundamental understanding of the cellular metabolism and accompanying epigenetic and phenotypic changes during in vivo and ex vivo expansion of T cells will be just as important. Such discoveries will provide an invaluable tool box from which actionable knowledge could be drawn for designing an adaptable CAR T production process that is able to absorb the patient-to-patient variation.