Treatment of solid tumors with chimeric antigen receptor-engineered T cells: current status and future prospects

Abstract

Chimeric antigen receptors (CARs) are artificial recombinant receptors that generally combine the antigen-recognition domain of a monoclonal antibody with T cell activation domains. Recent years have seen great success in clinical trials employing CD19-specific CAR-T cell therapy for B cell leukemia. Nevertheless, solid tumors remain a major challenge for CAR-T cell therapy. This review summarizes the preclinical and clinical studies on the treatment of solid tumors with CAR-T cells. The major hurdles for the success of CAR-T and the novel strategies to address these hurdles have also been described and discussed.

PSCA and MUC1 in non-small-cell lung cancer as targets of chimeric antigen receptor T cells

“…37, 38 The use of these few non-cancer-specific antigens, which include FAP, 39 EGFR, 40 mesothelin 41 and glypican-3, 17 has led to poor or undefined therapeutic outcomes in patients. It is therefore important to broaden the NSCLC-specific targets of CAR T cells.…”

Chimeric antigen receptor T cells: a novel therapy for solid tumors

“…The second and third generation of CARs including one activation domain and one or more costimulatory domains (CD28, 4-1BB, or OX40) were developed and contributed to the expansion, prolonged antitumor activity, and cytokine secretion (such as IL-2, TNFα, and IFN-γ) of T cell (Fig. 1) [7, 8]. Currently, anti-CD19 CAR-T cells were demonstrated to be effective in the treatment of B cell non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL) [9–13].…”

Tumor-Derived Extracellular Vesicles Impair CD171-Specific CD4+ CAR T Cell Efficacy

“…To date, the success of CAR T cell therapy has mostly been limited to the treatment of hematopoietic cancers (1)(2)(3)(4)(5). CAR T cell therapy for solid tumors can be hampered by an anti-inflammatory tumor microenvironment, which promotes immune escape mechanisms (6,7). Here, intercellular communication plays a crucial role in establishing a protumorigenic micromilieu that facilitates cancer spread and immune cell exclusion or dormancy (8).…”