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Advances in CAR T Cell Therapy for Non-Small Cell Lung Cancer

嵌合抗原受体 癌症研究 细胞疗法 医学 T细胞 免疫疗法 表皮生长因子受体 抗原 癌症 免疫学 干细胞 生物 内科学 免疫系统 细胞生物学
作者
Hong Ma,Jeeban P. Das,Conor Prendergast,Dorine de Jong,Brian Braumuller,Jacienta Paily,Sophia Huang,Connie Liou,Anna O. Giarratana,Mahdie Hosseini,Randy Yeh,Kathleen M. Capaccione
出处
期刊:Current Issues in Molecular Biology [MDPI AG]
卷期号:45 (11): 9019-9038 被引量:31
标识
DOI:10.3390/cimb45110566
摘要

Since its first approval by the FDA in 2017, tremendous progress has been made in chimeric antigen receptor (CAR) T cell therapy, the adoptive transfer of engineered, CAR-expressing T lymphocyte. CAR T cells are all composed of three main elements: an extracellular antigen-binding domain, an intracellular signaling domain responsible for T cell activation, and a hinge that joins these two domains. Continuous improvement has been made in CARs, now in their fifth generation, particularly in the intracellular signaling domain responsible for T cell activation. CAR T cell therapy has revolutionized the treatment of hematologic malignancies. Nonetheless, the use of CAR T cell therapy for solid tumors has not attained comparable levels of success. Here we review the challenges in achieving effective CAR T cell therapy in solid tumors, and emerging CAR T cells that have shown great promise for non-small cell lung cancer (NSCLC). A growing number of clinical trials have been conducted to study the effect of CAR T cell therapy on NSCLC, targeting different types of surface antigens. They include epidermal growth factor receptor (EGFR), mesothelin (MSLN), prostate stem cell antigen (PSCA), and mucin 1 (MUC1). Potential new targets such as erythropoietin-producing hepatocellular carcinoma A2 (EphA2), tissue factor (TF), and protein tyrosine kinase 7 (PTK7) are currently under investigation in clinical trials. The challenges in developing CAR T for NSCLC therapy and other approaches for enhancing CAR T efficacy are discussed. Finally, we provide our perspective on imaging CAR T cell action by reviewing the two main radionuclide-based CAR T cell imaging techniques, the direct labeling of CAR T cells or indirect labeling via a reporter gene.

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