Chimeric Antigen Receptor T-Cell Therapy for Colorectal Cancer

Abstract

Chimeric antigen receptor (CAR) T-cell therapy represents a new genetically engineered method of immunotherapy for cancer. The patient's T-cells are modified to express a specific receptor that sticks to the tumor antigen. This modified cell is then reintroduced into the patient's body to fight the resilient cancer cells. After exhibiting positive results in hematological malignancies, this therapy is being proposed for solid tumors like colorectal cancer. The clinical data of CAR T-cell therapy in colorectal cancer is rather scarce. In this review, we summarize the current state of knowledge, challenges, and future perspectives of CAR T-cell therapy in colorectal cancer. A total of 22 articles were included in this review. Eligible studies were selected and reviewed by two researchers from 49 articles found on Pubmed, Web of Science, and clinicaltrials.gov. This therapy, at the moment, provides modest benefits in solid tumors. Not taking into consideration the high manufacturing and retail prices, there are still limitations like increased toxicities, relapses, and unfavorable tumor microenvironment for CAR T-cell therapy in colorectal cancer.

Keywords: Chimeric antigen receptor (CAR)T-cell; colorectal cancer; immunotherapy; toxicity; trials.

Figure 1

Overview of chimeric antigen receptor (CAR) T-cell therapy. Process of extracting normal T-cells from the patient’s peripheral blood; integration of CARs in T-cells in the laboratory; in vitro cultivation and expansion of CAR T-cells that are re-infused into the patient’s bloodstream; CAR T-cells proliferate and kill the tumor cells that bear the specific antigen the CARs are directed against.

Figure 2

Targets for CAR T-cell therapy in CRC: Anti-4-1BB; CEA; guanylylcyclase2C (GUCY2C); TAG-72; EpCAM; epithelial glycoprotein 40(EGP40); NKG2D; HER-2; interferon alpha and beta receptor subunit 1(IFNAR1); prominin-1 (CD133); epithelial glycoprotein-2 (EGP-2).