CAR-T Cell Therapy in Cancer: Current Pros and Cons

tibbibiyolojiozel-2-2-24kapak

Cihan TAŞTANa,b, Gamze GÜLDENb,c, Berranur SERTb,c
aÜsküdar University Faculty of Engineering and Natural Science, Department of Molecular Biology and Genetics, İstanbul, Türkiye
bÜsküdar University Transgenic Cell Technologies and Epigenetic Application and Research Center (TRGENMER), İstanbul, Türkiye
cÜsküdar University Institute of Science and Technology, Department of Molecular Biology, İstanbul, Türkiye

Taştan C, Gülden G, Sert B. CAR-T cell therapy in cancer: Current pros and cons. In: Yar Sağlam AS, ed. Innovative Approaches in Cancer Diagnosis and Treatment. 1st ed. Ankara: Türkiye Klinikleri; 2024. p.59-70.

Makale Dili: EN

ABSTRACT
CAR-T cell therapy is a promising treatment for cancer that faces numerous challenges to achieve its full potential. One major obstacle is the lack of unique tumor-associated antigens (TAAs) in many cancers. Identifying and targeting TAAs that are expressed in cancer cells without harming healthy tissues is essential to avoid side effects. Moreover, CAR-T cells often struggle with persistence and proliferation post-transfer, inefficient binding to tumor sites, heterogeneous antigen expression, and the presence of immunosuppressive factors within the tumor microenvironment, which further limits their effectiveness. Researchers are exploring various strategies to overcome these issues. Enhancing the persistence and proliferation of CAR-T cells, improving their ability to infiltrate tumor sites, and selecting appropriate target antigens are critical steps. Incorporating immunostimulatory cytokines such as IL-2, IL-7, IL-15, and IL-12 can boost T cell activity and improve tumor destruction. Additionally, optimizing CAR designs, including suicide genes and smart CAR designs, can enhance safety and specificity. Overcoming the immunosuppressive tumor microenvironment is also crucial for CAR-T cell efficacy. Strategies to counteract immunosuppressive molecules and enhance T cell infiltration into tumors are being investigated. Furthermore, engineering CAR-T cells to release factors that modify the tumor microenvironment is necessary. Future steps involve developing CARs targeting new antigens, engineering CAR-T cells to release factors that modify the tumor microenvironment, and designing more effective CAR-T cells containing new synthetic genes. By addressing these challenges and fostering innovation, researchers aim to maximize the therapeutic potential of CAR-T cell therapy for solid tumors.

Keywords: Chimeric antigen receptor (CAR); cancer immunotherapy

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