Advances in promoting chimeric antigen receptor T cell trafficking and infiltration of solid tumors

Abstract

T cells engineered to express chimeric antigen receptors (CARs) have demonstrated robust response rates in treating hematological malignancies. However, solid tumors present multiple challenges that hinder the antitumor efficacy of CAR-T cells, including antigen heterogeneity, off-tumor and systemic toxicities, and the immunosuppressive milieu of the tumor microenvironment (TME). Notably, the TME of solid tumors is characterized by chemokine dysregulation and a dense architecture consisting of tumor stroma, extracellular matrix, and aberrant vasculature that impede migration of CAR-T cells to the tumor site as well as infiltration into the solid-tumor mass. In this review, we highlight recent advances to improve CAR-T-cell trafficking to and infiltration of solid tumors to promote effective antigen recognition by CAR-T cells.