Driving CAR T cells towards dermatologic oncology.

Whereas approximately half of metastatic melanoma patients benefit from combined immune checkpoint inhibition targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1), for those who do not respond, further strategies and treatment options need to be developed. Thus, focus is turning to the use of chimeric antigen receptor (CAR) T cells, a novel therapy that has not yet achieved a major breakthrough in solid tumors despite the impressive response rates reported for their use in hematologic malignancies. In melanoma and other solid tumor entities, different problems still need to be addressed to improve this therapy, with mechanisms to counteract tumor escape being one of them. In this context, we could show the feasibility of combining two different transfection methods - lentiviral transduction and RNA-electroporation - for equipping the same T lymphocyte with two different tumor antigen-specific receptors. While further analysis is required to transfer this novel strategy from bench to bedside, appropriate target antigens that avoid on-target/off-tumor toxicities and additional optimization to increase CAR T cell power are also needed to maximize their potential use in dermatologic oncology.