TY  - EJOU
AU  - Sun, Haijun 
AU  - Yan, Wenyue 
AU  - Li, Zhanyu 
AU  - Li, Qintian 
AU  - Du, Qilong 
AU  - Xu, Li 
AU  - Cao, Wanwei 
AU  - Yang, Junrong 
AU  - Yang, Xilan 
AU  - Chen, Jun 
AU  - Mao, Yuan 
AU  - Huang, Wen 

TI  - The Construction and Preclinical Evaluation of Antitumor Activity of a Novel MIgG-OXA ADC in Lung Adenocarcinoma
T2  - Oncology Research

PY  - 
VL  - 
IS  - 
SN  - 1555-3906

AB  - <b>Background:</b> The melanoma-associated antigen-A1 (MAGE-A1) demonstrates tumor-restricted expression patterns in diverse malignancies, positioning it as an attractive therapeutic target. This investigation aimed to engineer and validate a novel antibody-drug conjugate with oxaliplatin targeting MAGE-Al (MIg-OXA), a novel antibody-drug conjugate targeting MAGE-A1, while assessing its therapeutic potential against MAGE-A1-expressing lung adenocarcinoma through both cellular and animal models. <b>Methods:</b> We generated a MAGE-A1-specific immunoglobulin G (IgG) antibody (MIgG) and subsequently conjugated it with oxaliplatin (OXA) to produce MIgG-OXA. The conjugate’s binding specificity and cellular uptake were verified through cell-based enzyme-linked immunosorbent assay (ELISA), flow cytometric analysis, and immunofluorescence microscopy. Functional assessments included Cell Counting Kit-8 (CCK-8) viability assays, transwell migration studies, apoptosis detection, and antibody-dependent cell-mediated cytotoxicity (ADCC) evaluation to determine anti-neoplastic activity in cultured cells. Therapeutic efficacy in living organisms was examined using lung adenocarcinoma (LUAD) xenograft-bearing athymic mice. <b>Results:</b> Our data confirmed successful synthesis and validation of MIgG-OXA, which demonstrated selective recognition of MAGE-A1-expressing LUAD cell populations and facilitated controlled OXA release. When compared to unconjugated OXA, MIgG-OXA displayed enhanced tumor suppression in both cultured LUAD cells and transplanted tumor models. <b>Conclusion:</b> These findings collectively indicate that MIgG-OXA holds substantial promise as a precision therapeutic approach for patients harboring MAGE-A1-positive LUAD.
KW  - Melanoma-associated antigen-A1 (MAGE-A1); immunoglobulin G (IgG); oxaliplatin (OXA); antibody-drug conjugates (ADCs)

DO  - 10.32604/or.2026.080413