Chimeric antigen receptor T cells applied to solid tumors

Abstract

Chimeric antigen receptor T cell (CAR-T) therapy is novel tumor immunotherapy that enables autologous T to express synthetic receptors to specifically recognize the surface tumor-associated antigens for exerting subsequent antitumor effects, and eliminating the resistance, metastases and recurrence of cancer. Although CAR T cells have exhibited success in eradicating hematologic malignancies, their applications to solid tumors has not yet been achieved due to obstacles such as the immune-suppressor tumor microenvironment and lack of tumor specific target antigens. In this review, we presented advancements in the development of CAR T cell therapy in solid tumors, and offered a brief summary of the challenges, as well as novel engineering and pharmaceutical interventions to overcome these barriers. Looking forward, we discussed the latest studies which are expected to reach the clinicals in the next few years, including CRISPR screens-based CAR modification and CAR T cells driven from progenitor-like T cells. Collectively, this review may inspire researchers and clinicians to develop clinical available strategies of CAR T cell therapies in solid tumor.

Chimeric Antigen Receptor T Cell Therapy for Pancreatic Cancer: A Review of Current Evidence

“…Nevertheless, high hopes are associated with the prospective use of CAR-T strategy against solid cancers, especially the ones resistant to standard oncological therapies, such as PC. Indeed, current pre-clinical and clinical studies evaluate potential tumor-associated antigens (TAA), cancer markers, CAR-T cell toxicities, and efficacy in PC [ 56 , 57 ].…”

Progress on Phage Display Technology: Tailoring Antibodies for Cancer Immunotherapy

“…Despite the high efficacy demonstrated in hematological tumors, therapy with CAR-expressing cells still faces several challenges in its application to treat solid tumors [ 175 ]. One challenge is the infeasibility of completely depleting cells expressing the target antigen, as solid-tumor-associated antigens are often found in healthy cells of vital tissues.…”

“…One challenge is the infeasibility of completely depleting cells expressing the target antigen, as solid-tumor-associated antigens are often found in healthy cells of vital tissues. However, several proteins overexpressed in tumor cells have been tested as targets for CAR cell therapy [ 175 ], including mesothelin (MSLN), a membrane glycoprotein expressed in normal mesothelial tissues but highly expressed in various malignancies, such as non-small-cell lung cancer (NSCLC) and ovarian cancer. MSLN has been investigated as a target for CAR-T cells in treating solid tumors, including mesothelioma, lung, breast, and pancreatic cancer [ 175 , 176 ].…”

T cell-derived exosomes in tumor immune modulation and immunotherapy

“…Chimeric antigen receptor (CAR) T cells conjugate the antigen-binding part of an antibody that recognizes a tumor antigen and the intracellular part of the CD3-ζ chain or FcϵRIγ into a chimeric protein in vitro , and patient T cells are then transfected with gene transduction to express CAR ( 71 ). Patient T cells are “reprogrammed” to generate a large number of tumor-specific CAR-T cells, which have been successfully designed and used to treat malignant blood diseases ( 72 ).…”