How to Test Human CAR T Cells in Solid Tumors, the Next Frontier of CAR T Cell Therapy

Chimeric antigen receptor (CAR) T cell therapy has proven to be a successful treatment option for leukemias and lymphomas. These encouraging outcomes underscore the potential of adoptive cell therapy for other oncology applications, namely, solid tumors. However, CAR T cells are yet to succeed in treating solid tumors. Unlike liquid tumors, solid tumors create a hostile tumor microenvironment (TME). CAR T cells must traffic to the TME, survive, and retain their function to eradicate the tumor. Nevertheless, there is no universal preclinical model to systematically test candidate CARs and CAR targets for their capacity to infiltrate and eliminate human solid tumors in vivo. Here, we provide a detailed protocol to evaluate human CAR CD4⁺ helper T cells and CD8⁺ cytotoxic T cells in immunodeficient (NSG) mice bearing antigen-expressing human solid tumors.