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

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.