Targeted AAV Gene Therapy for Triple-Negative Breast Cancer: Anti-EGFR Monoclonal Antibody-Conjugated Exosomes
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Date
2025-05
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Publisher
The Ohio State University
Abstract
Triple-negative breast cancer (TNBC) is a highly aggressive and clinically challenging breast cancer subtype characterized by the absence of estrogen, progesterone, and HER2 receptors. The lack of these molecular targets limits the effectiveness of current therapies and contributes to poor patient prognosis and high recurrence rates. This study investigates a novel gene therapy approach that targets the mitochondria to selectively induce apoptosis in TNBC cells. The gene therapy mLumiOpto was designed to disrupt the inner mitochondrial membrane (IMM) potential, leading to cell death, and was delivered using adeno-associated virus (AAV) vectors. To overcome immunogenicity associated with AAV, vectors were encapsulated in exosomes. To then enhance delivery specificity, the AAV was conjugated to anti-EGFR monoclonal antibodies (mAb-Exo-AAV), as EGFR is overexpressed in multiple TNBC cell types. Comprehensive in vitro analyses confirmed successful delivery, TNBC-specific binding, appropriate nanoparticle size and morphology, and induction of cytotoxicity. These findings support the potential of mAb-Exo-AAV-mediated mLumiOpto delivery as a targeted and effective gene therapy strategy for TNBC.
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Keywords
Cancer, Monoclonal Antibodies (mAb), AAV Gene Therapy, Targeted Gene Therapy, Triple Negative Breast Cancer (TNBC), Exosomes