CAR T-cells for colorectal cancer immunotherapy: Ready to go?

Abstract

Chimeric antigen receptor (CAR) T-cells represent a new genetically engineered cell-based immunotherapy tool against cancer. The use of CAR T-cells has revolutionized the therapeutic approach for hematological malignancies. Unfortunately, there is a long way to go before this treatment can be developed for solid tumors, including colorectal cancer. CAR T-cell therapy for colorectal cancer is still in its early stages, and clinical data are scarce. Major limitations of this therapy include high toxicity, relapses, and an impermeable tumor microenvironment for CAR T-cell therapy in colorectal cancer. In this review, we summarize current knowledge, highlight challenges, and discuss perspectives regarding CAR T-cell therapy in colorectal cancer.

Keywords: CAR T cells; clinical data; colorectal cancer; immunotherapies; tumor microenvironement; tumor mutational burden.

Figure 1

Principles of chimeric antigen receptor (CAR) T-cell therapy/CAR T-cell manufacturing process. CAR T-cell production includes normal T-cell extraction from the patient’s peripheral blood, followed by enrichment and CAR vector delivery, using viral or non-viral vector systems, into the T-cells in vitro. The CAR T-cells is subjected to expansion before being re-injected into the patient’s bloodstream. Patients usually receive a lymphodepletion before CAR T-cell administration to improve the expansion of adoptively transferred T-cells. The CAR T-cells proliferate and attack tumor cells that carry the specific antigen against which the CARs are directed (Source: Author’s personal collection, 2021). Created with BioRender.com.

Figure 2

Active and passive immunotherapy strategies in colorectal cancer. The immunotherapy treatments approved in recent years has widened the arsenal against colorectal cancer. Active immunotherapy includes cancer vaccines, checkpoint inhibitors, and oncolytic viruses. Cancer vaccine immunotherapy approaches are based on immunizing patients with cancer against their autologous cancers using either autologous tumor cell-derived vaccines, dendritic cell vaccines, peptide vaccines, DNA vaccines, or viral vector vaccines. Passive immunotherapy includes the use of immune checkpoint blockade, cytokines, and adoptive cell transfer of ex vivo educated immune cells (Source: Author’s personal collection, 2021). Created with BioRender.com.