Cellular immunotherapy (non-engineered) (N/A)

Cellular immunotherapy with no discrete molecular drug target refers to a category of adoptive cell transfer (ACT) therapies, most notably tumor-infiltrating lymphocyte (TIL) therapy, where the therapeutic agent is a population of live immune cells rather than a molecule hitting a single protein [National Cancer Institute]. These therapies utilize the natural, polyclonal diversity of the patient's own T-cells to recognize a wide array of patient-specific neoantigens presented on the surface of tumor cells [Rosenberg & Restifo, 2015]. Unlike CAR-T cell therapies, which are engineered to target a specific surface antigen like CD19, non-engineered cellular immunotherapies rely on the endogenous T-cell receptors (TCRs) already present in the harvested cells [Nature Reviews Cancer, 2022]. This approach is particularly effective in high-mutation-burden cancers such as metastatic melanoma, as evidenced by the FDA approval of Lifileucel [FDA, 2024]. The treatment process typically involves harvesting cells from a tumor biopsy, expanding them ex vivo, and re-infusing them into the patient following a lymphodepleting chemotherapy regimen [Journal of Clinical Oncology, 2021]. While this modality offers a durable response in some patients, it is associated with significant toxicities including cytokine release syndrome, capillary leak syndrome, and prolonged cytopenia [StatPearls, 2023].

Other names

Adoptive cell transferTumor-infiltrating lymphocyte therapyTIL therapyNon-specific cellular immunotherapyAutologous immune cell therapy

Polyclonal T-cell recognition of multiple tumor-specific neoantigens and direct cell-mediated cytotoxicity [Rosenberg & Restifo, 2015; FDA, 2024].