Autologous tumor neoantigens (polyclonal, patient-specific)

Class

Autologous tumor-infiltrating lymphocyte (TIL) adoptive cell therapy

Pathway

Ex vivo expansion of a patient's own tumor-reactive T cells (recognizing tumor-specific/neo-epitope antigens), reinfused to mediate direct antitumor cytotoxicity

Tumor cells often acquire mutations that create neoantigens—altered proteins not found in healthy tissue. The immune system can recognize these as foreign, and many tumors already contain small numbers of T lymphocytes, called tumor-infiltrating lymphocytes (TILs), that have identified and moved toward these neoantigens. However, these TILs are typically too few or too suppressed within the tumor environment to clear the cancer. Autologous TIL therapy addresses this by surgically removing a piece of a patient's tumor, isolating the resident T cells, and growing them to very large numbers outside the body before reinfusing them into the same patient, usually after chemotherapy designed to deplete existing lymphocytes and create room for the expanded cells to engraft. The underlying rationale is to amplify a tumor-reactive immune response the body has already initiated, rather than introducing an entirely new therapeutic agent. Because the T cell receptors involved are polyclonal and patient-specific, this is an individualized rather than a fixed, off-the-shelf treatment. This approach is broadly relevant to solid tumors with enough somatic mutations to generate recognizable neoantigens, and is conceptually related to other immune-based cancer treatments that rely on unleashing or amplifying a patient's own antitumor immunity.