Neural stem cell delivery of oncolytic CRAd-S-pk7 immunotherapy for stage 3 ovarian cancer: Dose-regimen studies

Ovarian cancer (OVCA) is an aggressive and often recurrent malignancy with limited long-term responses to standard chemotherapy. To address the urgent need for novel, targeted therapies, we evaluated the efficacy of a tumor-tropic neural stem cell (NSC) platform delivering a conditionally replicative adenovirus (CRAd), NSC.CRAd-S-pk7, in preclinical models of advanced OVCA. A single intraperitoneal dose of NSC.CRAd-S-pk7 delivering 3 × 10 9 infectious units (IFUs) significantly reduced tumor burden and increased median survival by 33% (from 57 to 76 days) in immunocompetent mice, and 48% (from 54 to 80 days) in immunodeficient mice bearing OVCA peritoneal metastases. No observed adverse effects occurred at or below this dose. Optimization of the NSC transduction protocol enabled at least a 10-fold increase in CRAd-S-pk7 viral payload per cell, reducing the therapeutic cell dose by more than an order of magnitude—from 60 million to just 1 million NSCs. Repeated dosing further decreased tumor burden and increased median survival by 60% (from 57 to 91 days) in immunocompetent mice, suggesting a contribution from innate immune activation. These findings establish NSC.CRAd-S-pk7 as a promising oncolytic viro-immunotherapy treatment for advanced OVCA and support its advancement toward clinical translation.