Preclinical rationale for combining radiation therapy and immunotherapy beyond checkpoint inhibitors (i.e., CART)

An increasing appreciation for the role of the immune system in targeting cancer cells over the last decade has led to the development of several immunomodulatory agents aimed at enhancing the systemic antitumor immune response. One such method is the use of T cells that are genetically engineered to express chimeric antigen receptors (CARs). The remarkable success of this approach in advanced hematologic malignancies has garnered much enthusiasm for using this novel tool in treating other cancers. However, multiple challenges have hampered the application of this therapy to a broader set of solid tumors, most notably lung cancer. Immunotherapy has already shown great success in lung cancer, and is now the first-line treatment in PD-L1 expressing metastatic disease. Given the mounting evidence that radiation therapy plays a crucial role in amplifying the immune response elicited by immunomodulatory agents, there is potential for radiation to help in overcoming some of these challenges. In this review, we describe the basic principles of CAR T cell therapy and examine its successes and challenges to date. We then discuss the preclinical and clinical data supporting the use of radiation with immunomodulatory agents with a focus on preclinical rationale for combining CAR T cells and radiation therapy in future experiments with a focus on lung cancer.