An Introduction to T-cell Receptor T-cell (TCR-T) Therapy

The discussion compares 3 types of adoptive cell therapies in melanoma: TIL therapy, CAR T cells, and TCR-T cells. TIL therapy uses the patient’s own TILs grown in the lab, whereas CAR T relies on genetically modified T cells with engineered surface receptors, primarily effective in blood cancers. TCR-T therapy represents a newer approach that uses engineered T-cell receptors to recognize intracellular antigens in the context of MHC, showing early promise in melanoma for being easier to manufacture, potentially more effective, and less toxic than TILs.

Unlike monoclonal CAR T and TCR-T therapies that target specific antigens, TIL therapy is polyclonal and less predictable in terms of which tumor antigens it recognizes. Because of this uncertainty, regulatory approval for TIL products has required in vitro validation, such as demonstrating tumor cell killing through coculture assays. The complexity lies in determining whether these lab results translate to clinical effectiveness, especially when tumor-killing capacity may not be evident in vitro.

Despite in vitro variability, experts argue that the polyclonal nature of TILs—having been drawn from the patient’s tumor—suggests inherent specificity and potential in vivo efficacy. As TIL therapies evolve, refining their selection and characterization without overburdening regulatory pathways is seen as essential. Ensuring these innovative treatments remain accessible will depend on balancing scientific rigor with practical feasibility in clinical application.