Abstract
Chimeric antigen receptor T (CAR-T) cell therapy has exhibited a substantial clinical response in hematological malignancies, including B-cell leukemia, lymphoma, and multiple myeloma. Therefore, the feasibility of using CAR-T cells to treat solid tumors is actively evaluated. Currently, multiple basic research projects and clinical trials are being conducted to treat lung cancer with CAR-T cell therapy. Although numerous advances in CAR-T cell therapy have been made in hematological tumors, the technology still entails considerable challenges in treating lung cancer, such as on−target, of−tumor toxicity, paucity of tumor-specific antigen targets, T cell exhaustion in the tumor microenvironment, and low infiltration level of immune cells into solid tumor niches, which are even more complicated than their application in hematological tumors. Thus, progress in the scientific understanding of tumor immunology and improvements in the manufacture of cell products are advancing the clinical translation of these important cellular immunotherapies. This review focused on the latest research progress of CAR-T cell therapy in lung cancer treatment and for the first time, demonstrated the underlying challenges and future engineering strategies for the clinical application of CAR-T cell therapy against lung cancer.
Highlights
Lung cancer is one of the most frequently occurring malignant tumors worldwide and is characterized by a substantially high malignancy and poor prognosis [1]
Current clinical trials of CAR-T therapy against non-small-cell lung carcinoma (NSCLC) and small-cell lung carcinoma (SCLC) primarily focus on MSLN, MUC1, GPC3, PSCA, EGFR, CEA, HER2, PD-L1, ROR1, and other promising targets (Table 2)
Over the past few years, there has been a rapid increase in the use of CAR-T cell therapy to treat hematological malignancies and solid tumors
Summary
Lung cancer is one of the most frequently occurring malignant tumors worldwide and is characterized by a substantially high malignancy and poor prognosis [1]. The present therapeutic measures for NSCLC primarily include surgical resection, chemoradiation, molecular-targeted therapy, and immunotherapy [6]. Patient’s T cells are extracted, isolated, and genetically engineered to express a CAR on their surface, targeting tumor-specific antigens of cancer cells. CAR-T cells targeting CD19 have become a leading engineered T-cell therapy strategy against relapsed or refractory acute lymphocytic leukemia and B-cell non-Hodgkin lymphoma [26, 27]. Only targeting CD19 did not show considerable efficacy in most refractory multiple myeloma (MM) patients, partly due to the lower expression of CD19 on the cell surface of myeloma, and there is no FDA-approved CAR-T cell therapy against it [22, 32, 33]. The unprecedented achievements of CAR-T cell therapy in hematological malignancies have improved the use of CAR-T cells in various solid tumors
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