Overview of CAR-T-Cell Therapy in Non-Small Cell Lung Cancer

Overview of CAR-T-Cell Therapy in Non-Small Cell Lung Cancer
Hossein Maleknia,¹ Safoora Pakizehkar,^2,*
1. Bachelor's student, Microbiology group, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
2. Cellular and Molecular Endocrine Research Centre (CMERC), Research Institute for Endocrine Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Introduction: The use of CAR-T-cell therapy signifies a pioneering tactic in the fight against cancer. This article investigates the existing scenario and potential innovations in CAR-T-cell therapy, stressing non-small-cell lung cancer (NSCLC). However, obstacles such as antigen specificity, immunosuppressive tumor microenvironments, and toxicity management persist.
Methods: A systematic literature review was undertaken, concentrating on contemporary research and clinical trials pertinent to CAR-T-cell therapy in NSCLC. Information was gathered from scholarly journals were available on PubMed and Google Scholar, and pertinent literature to evaluate the architecture, development, and utilization of CAR-T cells.
Results: The genetic composition of CAR-T cells is carefully structured to manifest receptors that specifically correspond to tumor-associated antigens (TAAs). The design of CAR-T cells involves an extracellular domain for attaching to antigens, a hinge or spacer segment, a domain that crosses the membrane, and internal domains that are key for signaling. Recent advancements in the development of CAR generations have significantly improved T-cell activation and longevity. Regarding non-small cell lung cancer (NSCLC), several antigens have surfaced as targets: EGFR, MSLN, MUC1, PSCA, CEA, PD-L1, and CD80/CD86. Each of these antigens poses distinct challenges and opportunities for optimized targeting. Clinical investigations have demonstrated the potential effectiveness of CAR-T cells against these specific targets, albeit the aspects of safety and efficacy continue to be subjects of rigorous inquiry. Prominent challenges encompass on-target but off-tumor toxicity, neurological toxicity, cytokine release syndrome, and the phenomenon of tumor antigen escape. Approaches to mitigate these challenges involve the selection of antigens that are deemed safer, the optimization of CAR constructs, and the enhancement of T-cell infiltration and persistence within the tumor microenvironment.
Conclusion: The introduction of CAR-T-cell therapy indicates a key improvement in the care of non-small cell lung cancer (NSCLC), with a host of innovative practices now being examined closely. Ongoing scholarly inquiry and clinical trials remain imperative to surmount prevailing obstacles and to augment the therapeutic efficacy and safety profiles of CAR-T cells for patients afflicted with NSCLC. As novel methodologies and technological advancements materialize, the prospective landscape of CAR-T-cell therapy appears auspicious, instilling optimism for enhanced clinical outcomes in the context of NSCLC.
Keywords: NSCLC, CAR T Cell Therapy, Tumor-Associated Antigens