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ARTICLE

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

Haijun Sun1,#, Wenyue Yan2,#, Zhanyu Li3,#, Qintian Li4, Qilong Du4, Li Xu5, Wanwei Cao3, Junrong Yang6, Xilan Yang2, Jun Chen7,*, Yuan Mao4,8,*, Wen Huang4,*
1 Department of Thoracic Surgery, The First People’s Hospital of Lianyungang, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, China
2 Department of Geriatric Palliative Care, Thoracoabdominal Oncology Center, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, China
3 Department of Pathology, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
4 Department of Geriatric Oncology, Thoracoabdominal Oncology Center, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, China
5 Department of Pathology, Jiangsu Cancer Hospital, Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
6 Department of Pathology, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, China
7 Department of Respiratory Medicine, Jiangsu Province Geriatric Hospital, Geriatric Hospital of Nanjing Medical University, Nanjing, China
8 Department of Hematology and Oncology, Jiangsu Province Geriatric Hospital, Geriatric Hospital of Nanjing Medical University, Nanjing, China
* Corresponding Author: Jun Chen. Email: email; Yuan Mao. Email: email; Wen Huang. Email: email
# These authors contributed equally to this work as the first author

Oncology Research https://doi.org/10.32604/or.2026.080413

Received 09 February 2026; Accepted 18 May 2026; Published online 09 June 2026

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: These findings collectively indicate that MIgG-OXA holds substantial promise as a precision therapeutic approach for patients harboring MAGE-A1-positive LUAD.

Keywords

Melanoma-associated antigen-A1 (MAGE-A1); immunoglobulin G (IgG); oxaliplatin (OXA); antibody-drug conjugates (ADCs)

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