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

Publication Year:

2026

Authors:

Rachael Mooney, Gary Ngai, Gurmeet Kaur, Elaine Y Kang, Jacqueline Lara, Eslam E Abd El-Fattah, Patricia Huang, Linda Flores, Marisa McDonald, Min Talley, Mohamed Hammad, Michael Laidlaw, Ashley Alamillo, Duong Hoang Nguyen, Maciej S Lesniak, David T Curiel, Marcin Kortylewski, Antonio F Santidrian, Thanh Dellinger, Karen S Aboody

PubMed ID:

42179969

Public Summary:

Ovarian cancer is a difficult-to-treat disease that often comes back after standard chemotherapy. New treatment approaches are urgently needed, especially for patients with advanced cancer that has spread within the abdomen. This project evaluated a new cell-based therapy called NSC.CRAd-S-pk7, which uses tumor-seeking neural stem cells to deliver an oncolytic virus directly to ovarian cancer tumors. The virus is designed to selectively grow in and destroy cancer cells while limiting damage to normal tissues. In preclinical models of advanced ovarian cancer, treatment with NSC.CRAd-S-pk7 reduced tumor burden and extended survival in both immune-intact and immune-deficient mice. A single intraperitoneal dose increased median survival by 33% in immune-intact mice and 48% in immune-deficient mice. No adverse effects were observed at or below the therapeutic dose tested. We also improved the manufacturing approach so that each neural stem cell carried substantially more virus. This allowed the therapeutic cell dose to be reduced from 60 million cells to 1 million cells while maintaining anti-tumor activity. Repeated dosing produced even greater benefit, reducing tumor burden and increasing median survival by 60% in immune-intact mice. These results suggest that NSC.CRAd-S-pk7 may work both by directly killing tumor cells and by stimulating anti-cancer immune responses. Together, these findings support NSC.CRAd-S-pk7 as a promising new oncolytic viro-immunotherapy for advanced ovarian cancer and provide a strong foundation for moving this therapy toward clinical testing.

Scientific Abstract:

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 x 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.