MAGE-A1 in lung adenocarcinoma as a promising target of chimeric antigen receptor T cells

J Hematol Oncol. 2019 Oct 22;12(1):106. doi: 10.1186/s13045-019-0793-7.

Abstract

Background: Cancer/testis antigens (CTAs) are a special type of tumor antigen and are believed to act as potential targets for cancer immunotherapy.

Methods: In this study, we first screened a rational CTA MAGE-A1 for lung adenocarcinoma (LUAD) and explored the detailed characteristics of MAGE-A1 in LUAD development through a series of phenotypic experiments. Then, we developed a novel MAGE-A1-CAR-T cell (mCART) using lentiviral vector based on our previous MAGE-A1-scFv. The anti-tumor effects of this mCART were finally investigated in vitro and in vivo.

Results: The results showed striking malignant behaviors of MAGE-A1 in LUAD development, which further validated the rationality of MAGE-A1 as an appropriate target for LUAD treatment. Then, the innovative mCART was successfully constructed, and mCART displayed encouraging tumor-inhibitory efficacy in LUAD cells and xenografts.

Conclusions: Taken together, our data suggest that MAGE-A1 is a promising candidate marker for LUAD therapy and the MAGE-A1-specific CAR-T cell immunotherapy may be an effective strategy for the treatment of MAGE-A1-positive LUAD.

Keywords: CAR-T cell; Cancer/testis antigen; Lung adenocarcinoma; MAGE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / metabolism*
  • Animals
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Lung Neoplasms / metabolism*
  • Melanoma-Specific Antigens / genetics
  • Melanoma-Specific Antigens / metabolism*
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental
  • Receptors, Chimeric Antigen / immunology
  • T-Lymphocytes / metabolism*

Substances

  • MAGEA1 protein, human
  • Melanoma-Specific Antigens
  • Receptors, Chimeric Antigen