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

Abstract

BackgroundCancer/testis antigens (CTAs) are a special type of tumor antigen and are believed to act as potential targets for cancer immunotherapy.MethodsIn 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.ResultsThe 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.ConclusionsTaken 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.

CAR T-Cell Cancer Therapy Targeting Surface Cancer/Testis Antigens

“…Other, more well-described, CT antigens have been tested as potential CAR targets. MAGE-A1 was investigated as a possible target in the treatment of lung adenocarcinoma (LUAD) after immunostaining revealed a surface epitope of the antigen ( 37 ). A MAGE-A1-specific CAR showed cytotoxic activity both in vitro and in vivo , where it was able to infiltrate MAGE-A1-positive tumors and specifically target and inhibit LUAD xenograft growth in nude mice.…”

Co-stimulatory and co-inhibitory Immune Markers in Solid Tumors With MET Alterations

“…Its expression has also been associated with progression and survival in NSCLC, but the specific mechanism for this phenomenon remains unknown [ 45 , 46 ]. CT antigens are ideal targets for cancer immunotherapy, and MAGEA1 has been shown to be actionable in vitro and in vivo by chimeric antigen receptor (CAR) T-cell therapy in lung adenocarcinoma cells, where the lung adenocarcinoma cells were effectively destroyed by IFN-γ secretion due to MAGEA1 inhibition [ 47 ]. Thayaparan et al reported that treatment of MET -expressing malignant mesothelioma cells with MET-retargeted CAR T cells was associated with significant IFN-γ release and tumor cell destruction [ 48 ].…”

Epigenetic Upregulation of MAGE-A Isoforms Promotes Breast Cancer Cell Aggressiveness

“…Although various cancers demonstrate MAGE-A family gene overexpression and the accumulation of their encoded proteins [19][20][21][22][23][24][25][26][27][28], the specific MAGE-A gene products that…”

“…Although various cancers demonstrate MAGE-A family gene overexpression and the accumulation of their encoded proteins [19][20][21][22][23][24][25][26][27][28], the specific MAGE-A gene products that are functionally relevant in breast cancer remain largely undetermined. To address this, we first analyzed the RNA-seq data of 70 breast cancer cell lines to determine the breast-cancer-related expression patterns of the MAGE-A gene family members.…”

“…Indeed, it was reported that different members of the MAGE-A gene family are upregulated in various types of cancers [19][20][21][22][23][24][25][26][27][28]. For example, MAGEA1 is upregulated in lung cancer, melanoma, and gastric cancer; MAGEA3 is upregulated in breast and lung cancer; MAGEA4 is upregulated in melanoma; MAGEA5 is upregulated in head and neck cancer; and MAGEA9 is upregulated in liver and colon cancer.…”