Oncolytic Viral Therapy for Breast Cancer
Abstract
Background: Integrin beta1 receptor is a type of protein expressed on the surface of tumor cells and macrophages in the tumor. Its high expression plays an important role in triple-negative breast cancer (TNBC) growth as well as resistance to therapy. There is an antibody that binds to this protein and blocks its function, which is currently being tested in patients with cancer as a therapy. Oncolytic viruses are engineered viruses that can replicate and destroy cancer cells. An oncolytic virus is currently FDA-approved and marketed for the treatment of melanoma. Ways to improve next-generation viruses for treatment of other cancers, including breast cancer, continue to be developed. Overarching Challenge: Combination therapy strategies that work with each other have the potential to reduce cancer burden while minimizing toxicities. In supporting data, we show that combination of oncolytic HSV with antibody against integrin beta 1 improves responses in mice bearing breast cancer. Antibody penetration in high enough concentrations to target tumor sites is a challenge and thus ways to locally deliver the antibody would also be a strength. Here we propose to develop a new kind of oncolytic virus that can also secrete an antibody that will target integrin beta 1 on cancer cells and in the tumor microenvironment. This will overcome challenges of systemic antibody delivery. We believe this will be more efficacious and safer. Type of Patients: The proposal will create and test this therapy for patients with TNBC. Breast cancer is the most commonly diagnosed cancer in women in the United States, excluding skin cancers. While advances in detection, diagnosis, and treatment have been made, it is estimated that over 41,000 women will die of this disease. According to data from Data from the Automated Central Tumor Registry (ACTUR) of the DoD and the nine cancer registries of the Surveillance, Epidemiology and End Results (SEER) of the National Cancer Institute, military women on active duty have a much higher risk of developing breast cancer. Thus, development of ways to combat this deadly disease is important. Potential Clinical Applications and Benefits: The proposed oncolytic virus can replicate in tumor cells and destroy cancer cells. During this lytic destruction, it will also produce an antibody fragment that can block integrin beta 1 on cancer cells and cancer-supporting normal cells in the tumor environment. This will permit the localized release of an antibody, bypassing challenges of delivery and potential toxicity associated with systemic antibody therapies. Projected Time: The projected time for this application is 3 years. At the end of this study, we will be in a position to pursue Good Manufacturing Practice production of the vector to bring it to patients for evaluation. Impact on BCRP’s Mission: The mission of BCRP is to “seeks to accelerate high-impact research with clinical relevance, encourage innovation and stimulate creativity, and facilitate productive collaborations.” The current proposal aims to create a novel therapeutic virus that will generate a new drug to fight cancer. Interim Outcomes: Based on this proposal, we will know if this virus shows improved therapeutic efficacy in vivo. The next steps would then be its clinical development, which includes large-scale production of clinical grade virus and detailed toxicity, stability, and biodistribution studies prior to evaluating it for safety and efficacy in patient populations.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110069
Entities
People
- Michael Lewis
Organizations
- Baylor College of Medicine
- United States Army