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

• Published in: Current Issues in Molecular Biology Vol. 45; no. 11; pp. 9019 - 9038
• Main Authors: Ma, Hong, Das, Jeeban, Prendergast, Conor, De Jong, Dorine, Braumuller, Brian, Paily, Jacienta, Huang, Sophia, Liou, Connie, Giarratana, Anna, Hosseini, Mahdie, Yeh, Randy, Capaccione, Kathleen
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.11.2023
• Subjects: Antigens; Antimitotic agents; Antineoplastic agents; B cells; Cancer; CAR T cell therapy; Development and progression; Drug approval; Drug therapy; Epidermal growth factor; Erythropoietin; imaging; Lung cancer, Non-small cell; Lung cancer, Small cell; Mucins; non-small cell lung cancer; NSCLC; Oncology, Experimental; solid tumors; Stem cells; T cells; Tyrosine; non-small cell lung cancer; CAR T cell therapy; NSCLC; imaging; solid tumors
• ISSN: 1467-3045; 1467-3037; 1467-3045
• DOI: 10.3390/cimb45110566

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.