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

中文翻译：

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肺腺癌中的MAGE-A1作为嵌合抗原受体T细胞的有希望的靶标。

癌症/睾丸抗原（CTAs）是一种特殊类型的肿瘤抗原，被认为可以作为癌症免疫疗法的潜在靶标。在这项研究中，我们首先针对肺腺癌（LUAD）筛选了合理的CTA MAGE-A1，并通过一系列表型实验探索了MAGE-A1在LUAD发育中的详细特征。然后，我们根据之前的MAGE-A1-scFv，使用慢病毒载体开发了新型MAGE-A1-CAR-T细胞（mCART）。最终在体外和体内研究了该mCART的抗肿瘤作用。结果表明，MAGE-A1在LUAD发生中表现出惊人的恶性行为，这进一步证实了MAGE-A1作为LUAD治疗靶点的合理性。然后，成功构建了创新的mCART，并且mCART在LUAD细胞和异种移植物中显示出令人鼓舞的肿瘤抑制功效。