Combine antibody-drug conjugate with cmLumiOpto for triple-negative breast cancer treatment
Year: 2026
Type: article
Abstract: Triple-negative breast cancer (TNBC) is an aggressive and chemotherapy-resistant subtype characterized by high metastatic potential and frequent recurrence, making monotherapies largely ineffective. This study evaluates a combination strategy utilizing a CD276 (B7-H3)-targeted antibody-drug conjugate (ADC) alongside mitochondria-targeted gene therapy. The anti-CD276 monoclonal antibody-mertansine conjugate substantially reduces tumor burden at a low dose. It exhibits strong synergy with the cmLumiOpto platform, enhancing cytotoxicity across three TNBC cell lines, impairing mitochondrial function, and elevating the tumoral immune response. Furthermore, the ADC/cmLumiOpto combination suppresses TNBC metastasis in mouse models and inhibits tumor growth by 95%-100% in patient-derived xenograft models. Mechanistic investigations reveal downregulated metastatic signaling, tumor microenvironment remodeling, increased apoptosis, and upregulated tumoral immunity. Histological and body weight analyses indicate minimal systemic toxicity. These findings highlight the translational potential of combining CD276-targeted ADC with mitochondrial gene therapy to treat aggressive TNBC.
Source: Cell Reports Medicine
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,620
Awards: Dual-payload antibody-drug conjugate for chemo-immunotherapy of triple-negative breast cancers, Resource for Native Mass Spectrometry Guided Structural Biology, Native Mass Spectrometry Guided Structural Biology Center, Cancer Center Support Grant, Combine mitochondrial gene therapy and synthetic lethal chemotherapy to treat triple-negative breast cancer, Delineate the Pathophysiological Effect of Cardiomyocyte-specific Mitochondrial Stress
OpenAlex ID: W7170819185