Cancer Immunotherapy: Challenges and Advancements in CAR T Cell Technology

Abstract

Cancer, characterized by uncontrolled cell proliferation, poses a major global health threat, as evident in the 2022 World Health Organization-International Agency for Research on Cancer report, recording 20 million new cases and 9.7 million deaths worldwide. Thailand alone reported 183,000 new cases and 118,000 fatalities, underscoring the need for tailored prevention, early detection, and treatment strategies. Conventional therapies like surgery, radiation, and chemotherapy, while effective in early stages, face limitations in advanced cases, prompting the development of targeted therapies and immunotherapy, notably chimeric antigen receptor (CAR) T cell therapy. CAR T cell therapy employs genetic engineering to create receptors recognizing cancer-specific antigens. Despite successes in hematological malignancies, challenges such as toxicities, relapse, and high costs persist. Ongoing research, led by the Siriraj Center of Research Excellence for Cancer Immunotherapy (SiCORE-CIT), focuses on advancing fourth- and fifth-generation CAR T cell technologies. SiCORE-CIT’s fourth-generation CAR T cells exhibit potent anti-tumor activity against various cancers, surpassing second-generation counterparts. The innovative fifth-generation “Siriraj fifth-generation CAR T cells” secrete anti-PD-L1 scFv, showing potential for diverse cancer applications, highlighting the transformative impact of ongoing research. Successful applications of fifth-generation CAR T cells in B-cell leukemia, lymphoma, and multiple myeloma underscore their transformative potential. This emphasizes the critical role of continuous research in refining therapeutic approaches for both hematologic and solid malignancies. The ongoing exploration and development in this domain have the potential to revolutionize cancer treatment paradigms, significantly contributing to alleviating the global health burden associated with this complex disease.