A narrative review of chimeric antigen receptor-T (CAR-T) cell therapy for lung cancer

Abstract

Lung cancer represents one of the most common and deadliest cancers in the world. Chimeric antigen receptor-T cell (CAR-T) therapy which can recognize antigens in a major histocompatibility complex (MHC)-independent manner provides a new approach for tumor treatment. However, lung cancer, as a solid tumor, faces several formidable barriers to adoptive cell transfer, which includes inhibition of T-cell localization and suppression of T-cell function. Therefore, lung cancer fails to respond significantly to infusions of CAR-T cells in most trials until now. PubMed was researched using the terms "CAR-T" and "lung cancer" only in English from 2000 through June 2020. We also included results presented in international conferences, such as the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO). Besides, we found new progress in CAR-T therapy for solid tumors as a supplement. To enhance the efficacy and conquer the limitations, we collected some applications in lung cancer. In recent years, there have been some improvements in selecting the proper target and reducing toxicity. CAR-T technology provides an excellent way for tumor treatment, which does not depend on MHC molecules and provides a new method for the utilization of tumor targets. Targeting different antigens and overcoming the solid barrier, there are some improvements in responding significantly and reducing toxicity. CAR-T technology will play a decisive role in the treatment of lung cancer.

Chimeric antigen receptor-T cells are effective against CEACAM5 expressing non-small cell lung cancer cells resistant to antibody-drug conjugates

“…CEACAM5, a glycosylated transmembrane protein, is often presented in lung cancer tumor tissues (42). CEACAM5-targeted therapies, including CAR-T cells (43) or ADCs (20), have been developed against lung cancer. Here, we investigated the efficacy of such therapeutic modalities targeting CEACAM5 in ADC-sensitive and -resistant NSCLC cell lines.…”

Regional delivery of mesothelin-targeted chimeric antigen receptor T-cell effectively and safely targets colorectal cancer liver metastases in mice

“…However, the published literature of the therapeutic effect of CAR T-cells in solid tumors shows their efficacy is unfortunately impeded by T cell homing and infiltration into the tumor ( 13 ). Regional delivery of CAR T-cells, such as intrapleural, intracranial, and intraperitoneal administration has demonstrated superior antitumor response and safety compared to systemic administration ( 14 - 16 ).…”

Chemokine Receptors CCR6 and PD1 Blocking scFv E27 Enhances Anti-EGFR CAR-T Therapeutic Efficacy in a Preclinical Model of Human Non-Small Cell Lung Carcinoma

“…Multiple CAR-T cell products were approved by the Food and Drug Administration (FDA) by the year 2022 [ 11 , 12 , 13 ]. Their use in solid tumor research is still ongoing [ 14 ], but many preclinical studies have demonstrated superior efficacy in the treatment of solid tumor models, including glioblastoma [ 15 ], sarcoma [ 16 ], neuroblastoma [ 17 ], breast cancer [ 18 ], advanced gastric or pancreatic cancer [ 19 ], lung cancer [ 20 ], hepatocellular carcinoma [ 21 ], ovarian cancer [ 22 ], and prostate cancer [ 23 ]. Clinical trials of CAR-T therapy targeting mesothelin (MSLN) [ 24 ], epidermal growth factor receptor (EGFR) [ 25 ], human epidermal growth factor receptor 2 (HER2) [ 26 ], and carcinoembryonic antigen (CEA) [ 27 ] in NSCLC have been completed in recent years, but with disappointing results.…”