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CmLumiOpto gene therapy in combination with chemotherapy to treat triple negative breast cancer.

ABSTRACT: Triple-negative breast cancer (TNBC) is aggressive, resistant to chemotherapy, and prone to recurrence. While PARP inhibitors (PARPi) help some patients, most do not respond. We developed a novel therapy combining mitochondria-targeted luminoptogenetics (cmLumiOpto) with PARPi to enhance treatment. Delivered via an anti-CD276 monoclonal antibody-conjugated exosome-AAV (mAb-Exo-AAV), cmLumiOpto disrupts mitochondrial membrane potential, inducing cancer cell death. In vitro, the combination increased cytotoxicity; in vivo, it reduced tumor burden by 95–100%, suppressed xenograft growth, and blocked metastasis in TNBC models. Mechanistic studies showed mitochondrial depolarization, DNA damage, cytokine release, and immune infiltration, highlighting a promising strategy for TNBC therapy. The mechanism of action was further explained through bulk RNA sequencing post-treatment. These findings highlight the therapeutic potential of our cmLumiOpto gene therapy for treatment of triple negative breast cancers.

ORGANISM(S): Mus musculus

PROVIDER: GSE305990 | GEO | 2026/01/12

REPOSITORIES: GEO

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