Engineered Cellular Therapies for the Treatment of Thoracic Cancers

Thoracic malignancies (lung cancers and malignant pleural mesothelioma) are prevalent worldwide and are associated with high morbidity and mortality. Effective treatments are needed for patients with advanced disease. Cell therapies are a promising approach to the treatment of advanced cancers that make use of immune effector cells that have the ability to mediate antitumor immune responses. In this review, we discuss the prospect of chimeric antigen receptor-T (CAR-T) cells, natural killer (NK) cells, T cell receptor-engineered (TCR-T) cells, and tumor-infiltrating lymphocytes (TILs) as treatments for thoracic malignancies. CAR-T cells and TILs have proven successful in several hematologic cancers and advanced melanoma, respectively, but outside of melanoma, results have thus far been unsuccessful in most other solid tumors. NK cells and TCR-T cells are additional cell therapy platforms with their own unique advantages and challenges. Obstacles that must be overcome to develop effective cell therapy for these malignancies include selecting an appropriate target antigen, combating immunosuppressive cells and signaling molecules present in the tumor microenvironment, persistence, and delivering a sufficient quantity of antitumor immune cells to the tumor. Induced pluripotent stem cells (iPSCs) offer great promise as a source for both NK and T cell-based therapies due to their unlimited expansion potential. Here, we review clinical trial data, as well as recent basic scientific advances that offer insight into how we may overcome these obstacles, and provide an overview of ongoing trials testing novel strategies to overcome these obstacles.