Advances and Hurdles in CAR T Cell Immune Therapy for Solid Tumors.

ABSTRACT

Chimeric antigen receptor (CAR) T cells in solid tumors have so far yielded limited results, in terms of therapeutic effects, as compared to the dramatic results observed for hematological malignancies. Many factors involve both the tumor cells and the microenvironment. The lack of specific target antigens and severe, potentially fatal, toxicities caused by on-target off-tumor toxicities constitute major hurdles. Furthermore, the tumor microenvironment is usually characterized by chronic inflammation, the presence of immunosuppressive molecules, and immune cells that can reduce CAR T cell efficacy and facilitate antigen escape. Nonetheless, solid tumors are under investigation as possible targets despite their complexity, which represents a significant challenge. In preclinical mouse models, CAR T cells are able to efficiently recognize and kill several tumor xenografts. Overall, in the next few years, there will be intensive research into optimizing novel cell therapies to improve their effector functions and keep untoward effects in check. In this review, we provide an update on the state-of-the-art CAR T cell therapies in solid tumors, focusing on the preclinical studies and preliminary clinical findings aimed at developing optimal strategies to reduce toxicity and improve efficacy.