Engineering a Biological Agent to Boost Brain Tumor Immunity
Abstract
Our proposed research addresses two Fiscal Year 2020 Peer Reviewed Cancer Research Program Topic Areas: brain cancer (primary), and pediatric brain tumors (secondary). Nearly 65% of brain cancer patients die within 5 years of diagnosis, a statistic that has not improved over the last 30 years. Even survivors suffer from debilitating defects in brain functions. While recently developed immunotherapy has been overwhelmingly successful in treating many types of tumors, clinical trials in brain tumors has not been successful, most likely due to two unique situations in brain tumors: first, the key anti-tumor immune cells called T cells cannot enter the brain, and second, even if they enter, the environmental factors in brain tumors are not supportive for T cell activities. In this grant application, we propose to harness a brain-tropic biological agent to solve both problems at once, by attracting T cells into brain tumors while creating a supportive brain environment for T cells. We also plan to engineer the biological agent to ensure its safety without compromising its effectiveness in boosting immunity. The knowledge gained here will inform us how the brain immune system can be activated to mount anti-tumor responses, which could lead to a paradigm shift in therapeutic strategies for brain cancer. Upon the completion of this project, we envision follow-up studies to test the combinatorial treatment between our agent and the current immunotherapy agents to determine if the combination will vastly increase the immune responses against brain tumors, which will take around 2 years. If successful, we should then move into clinical trials to assess the safety and efficacy of this treatment strategy in brain tumor patients, expecting not only to fundamentally improve survival but also to significantly enhance life quality. Active military members and Veterans run a higher risk of brain tumors than the general public, because the exposure to carcinogens during combat could cause brain injuries and gene mutations in brain cells that increase the risk of brain tumors. Furthermore, the exposure to chemicals and radioactive materials on the battlefield could lead to germline mutations that increase the risk of brain tumors in their children. The overall negative impact of brain tumors to patients and their families is tremendous. Therefore, the successful completion of this study would positively impact the readiness of Service Members and their family members.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110580
Entities
People
- Hui Zong
Organizations
- United States Army
- University of Virginia