Dr Faries on Emerging CAR T-Cell and TCR Cell Therapies in Melanoma

“[CAR T-cell and TCR cell therapies] are hopefully the next generation of TIL [therapies]. Those are cells that are engineered outside of the body to become melanoma specific. There aren’t any therapies that have crossed the line to prove efficacy, but there are encouraging candidates.”

Mark Faries, MD, surgical oncologist, Cedars‑Sinai, The Angeles Clinic and Research Institute; associate director, Surgical Oncology Experimental Therapeutics, Cedars Sinai Department of Surgery; and head, surgical oncology, Cedars-Sinai Medical Center, discusses how CAR T-cell therapies and transgenic T-cell receptor (TCR) cell therapies compare with current tumor-infiltrating lymphocyte (TIL) approaches in melanoma.

CAR T-cell and TCR therapies represent potential advancements over other adoptive cell therapies in melanoma, Faries begins. TIL therapy relies on naturally occurring lymphocytes that have infiltrated the tumor, recognizing melanoma cells through the body’s innate immune response, he explains. These cells are harvested, expanded ex vivo, and reinfused to enhance their antitumor activity, he says.

In contrast, CAR T-cell and transgenic TCR therapies involve genetic engineering to create tumor-specific immune cells, Faries states. Unlike TIL therapy, which requires tumor-infiltrating cells, these approaches utilize peripheral blood lymphocytes that are modified in the laboratory to specifically recognize melanoma-associated antigens, he details. CAR T-cell therapy employs chimeric antigen receptors to enable T cells to target surface antigens, whereas transgenic TCR therapy engineers T cells to recognize intracellular tumor antigens presented by major histocompatibility complex molecules, Faries explains.

Although these engineered cell therapies are still under investigation in melanoma, they offer potential advantages over TIL therapy, including broader applicability, more precise targeting, and the ability to circumvent immune evasion mechanisms, Faries says. No CAR T-cell or transgenic TCR therapies have yet demonstrated definitive efficacy in melanoma, but ongoing trials are evaluating several candidates that could enhance treatment options in the future, Faries concludes.