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Endogenous T Cell Therapy (ETC) is an advanced immunotherapy approach that enhances the body's natural immune response to target diseases, particularly cancer. Unlike traditional T cell therapies that rely on genetic modification (CAR-T) or tumor biopsy (TIL), ETC stimulates and expands a patient’s existing T cells from the peripheral blood, leveraging their natural ability to recognize and fight diseased cells. This method aims to improve treatment efficacy while reducing the complexities and costs associated with engineered cell therapies like CAR-T. ETC is being explored for various applications, including oncology and infectious diseases, with ongoing research focused on optimizing its memory function and anti-tumor activity to enhance clinical outcomes.

ETC therapy is a cell therapy modality pioneered by Dr. Cassian Yee who, together with Mark Davis and Peter Lee, first demonstrated the existence of circulating tumor-reactive T cells in patient peripheral blood. Subsequently, Dr. Yee treated the first cohort of metastatic melanoma patients with T cell clones he isolated and expanded from the peripheral blood, resulting in several durable clinical responses . A hallmark of ETC therapy is the absent requirement for high dose lymphodepletion or high dose IL-2 because of the intrinsic memory properties of the ETC T cell product first demonstrated as a correlate of clinical response and has subsequently become the foundation for combination based strategies for the treatment of solid tumors

• Cassian Yee, M.D., professor of Melanoma Medical Oncology and Immunology, and co-leader of the ACT platform, has pioneered the use of endogenous T-cell therapy for treating cancer. He spoke with Cancer Frontline about those efforts.

• Immunotherapy, which stimulates the patient’s own immune system to attack cancer, has shown promise in treating a variety of cancer types with long-term responses. This class of therapy involves a range of treatments, including checkpoint blockade inhibitors, vaccines and cell-based therapies.