Chimeric antigen receptor-modified cells for the treatment of solid tumors: First steps in a thousand-mile march

Chimeric antigen receptor (CAR)-engineered T-cell therapy is a promising cancer treatment strategy that harnesses the power of immunotherapy and exploits precision medicine. It consists of the genetic reprogramming of a patient’s own T lymphocytes to express a synthetic receptor that recognizes a specific tumor antigen while transducing signals that activate the T cells and hence mediate tumor killing. CAR T-cells demonstrated unprecedented durable responses in otherwise refractory hematologic malignancies and have been approved by the Food and Drug Administration for the treatment of acute lymphoblastic leukemia, diffuse large B cell lymphoma, mantle cell lymphoma, and multiple myeloma. Despite early promising results, consistent and reproducible clinical gains from CAR T-cell therapy in solid tumors have not yet been demonstrated. In this chapter, we summarize the results of the clinical trials investigating the use of CAR T-cell therapy in the treatment of a variety of solid cancers and discuss the obstacles encountered while shedding light on innovative strategies that may lead to success. We also briefly highlight the ongoing research harnessing the potential of other immune cells in CAR engineering for the treatment of solid tumors.