Strategies to improve CAR-T cell therapy for solid tumors
CAR-T cell therapy has achieved remarkable results by inducing high rates of sustained complete remissions in several hematologic malignancies, changing the paradigm of cancer treatment. Unfortunately, this success has not been recapitulated yet in the solid tumor setting, where objective clinical responses have been anecdotal and not durable. In spite of this, clinical experiences so far suggest that CAR-T cells are able to traffic to tumor sites, recognize and react against their target antigens, but they fail to persist, expand, and mediate productive and durable responses. Compared to hematologic malignancies, solid tumors pose extra barriers of complexity that CAR-T cells encounter upon arrival to tumors and need to overcome in order to be efficacious. Here, I will discuss such barriers and present new approaches to enhance the efficacy of CAR-T cells in the context of solid tumors, focusing on T cell extrinsic factors such as immunosuppression and tumor microenvironment.