Neural stem cell delivery of oncolytic CRAd-S-pk7 immunotherapy for stage 3 ovarian cancer: Dose-regimen studies
Year: 2026
Type: article
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 × 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.
Source: Molecular Therapy Oncology
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
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,900
Awards: G1076397280, G5121689744
OpenAlex ID: W7155792490
