Radiotherapy to Enhance Chimeric Antigen Receptor T-Cell Therapeutic Efficacy in Solid Tumors

IMPORTANCE: Immunotherapy has emerged as a new pillar of cancer therapy over the past decade. Adoptive immunotherapy in particular has become a major area of research interest, with advances seen in the development of T-cell engineering. As a result, chimeric antigen receptor (CAR) T-cell therapy has become a new and highly effective treatment option, especially for patients with refractory or resistant blood cell cancers. However, CAR T-cell therapy has shown limited efficacy for the treatment of solid tumors thus far. OBSERVATIONS: Combinatorial treatment approaches, such as addition of radiotherapy to CAR T cells, may provide a strategy to prevent resistance to CAR T-cell therapy of solid tumors. These approaches need to overcome obstacles that include abnormal vessels and adhesion molecule expression on tumor vasculature, leading to reduced transmigration of effector immune cells, including CAR T cells, and immunosuppressive cues in the tumor microenvironment, including regional hypoxia. CONCLUSIONS AND RELEVANCE: This review provides an overview of the current developments in CAR T-cell therapy and highlights the unique opportunities and challenges in combining CAR T-cell therapy with radiotherapy.