Emerging Immunotherapeutic Approaches in Colorectal Cancer: From Checkpoint Inhibitors to CAR-T Cell and Viral Vector...

Colorectal Cancer has been a significant health issue at a global level in terms of increasing incidence, high metastatic capacity, and inadequate treatment reactions in most patient groups. Though chemotherapy and targeted agents have given better survival chances, resistance to treatment, avoidance of the immune system as well as systemic toxicity still limit long-term efficacy. Immunotherapeutic strategies have developed as effective methods in the past few years to address these shortomings.

A comprehensive literature search was conducted across different electronics databases including Web of Science, PubMed, Scopus, and ScienceDirect utilizing keywords colorectal cancer immunotherapy, PD-1 / PD-L1, CAR-T cells, viral vector vaccines, carcinoembryonic antigen alone and in combinations.

PD-1/PD-L1, CTLA-4, immune checkpoint inhibitors have shown long-term responses, especially in mismatch repair-deficient and microsatellite instability-high tumours, and cell-based therapies such as CAR -T cells and dendritic cell vaccines provide other opportunities of personalised immune modulation.

This critical review summarizes the current developments in terms of immunotherapy and interventions of CRC with a focus on the mechanistic understanding of the issue, clinical outcomes, and combinatorial strategies aimed to improve antitumor immunity and surmount therapy resistance. Specific attention is paid to the optimization of the checkpoint blockade, innovations with vaccines and CAR-T engineering to accumulate and release tumor-specific cells and control the microenvironment. Finally, key translational challenges current clinical trials, and future perspectives are identified to promote the development of the next-generation multimodal therapies in the efficient and customized management of CRC.