Immunotherapeutic Targeting of Glioblastoma with Oncolytic Virus and Listeria-Based Anticancer Vaccine
Abstract
Scientific Objective and Rationale: Glioblastoma is a deadly brain cancer with limited overall survival and no effective clinical treatments available. Therefore, there is a critical need to develop new, safe, and effective treatment strategies for patients with this type of brain cancer. Cancer immunotherapy represents a promising treatment approach that will harness the patient’s immune system to attack and destroy tumors. This type of strategy is intended to be a safer and more effective alternative to the standard aggressive and toxic treatment options currently available to patients. Immunotherapy relies upon specifically activating immune responses to distinct targets that are found within cancer lesions, but clinical efforts to date with glioblastoma have been disappointing since not everyone is eligible (due, for example, to the lack of immune targets) or only transient protective benefits are achieved. The major objective of our proposed studies is to develop a new immunotherapeutic approach for glioblastoma that overcomes many of the current clinical limitations. Our proposed immunotherapeutic strategy will not only directly kill tumor cells, but also drive destructive immune responses against tumor-derived blood vessels, which allow tumor cells to grow and spread. Ultimately, we hypothesize that regardless of prior unsuccessful treatments, immunotherapy against BOTH tumor cells and tumor-derived blood vessels will revert cancer growth and provide long-lasting protection against glioblastoma. Career Goals and Development: The Principal Investigator’s (PI’s) career goals are to (i) advance an independent career in brain cancer research and (ii) develop a novel translational research program in immunotherapy for brain cancer. Although the PI has significant experience in tumor immunology and developing cancer immunotherapies using oncolytic viruses, the PI has expanded the scope of his work by combining oncolytic virus with a Listeria-based anti-cancer vaccine and/or a novel multi-functional bispecific anti-cancer antibody that is designed to effectively destroy BOTH cancer cells as well as tumor-derived blood vessels. This award will, therefore, provide the opportunity to develop an innovative research program in brain cancer where these new synergistic anti-cancer immunotherapy strategies (as outlined in the proposal) have not been previously applied. Overall, this funding mechanism will advance the PI’s career in the Fiscal Year 2019 (FY19) Peer Reviewed Cancer Research Program (PRCRP) Topic Areas of brain cancer, immunotherapy, and Listeria-based vaccines for cancer. The PI will be mentored by a team of independent and established cancer scientists (typified by significant publications, patents, funding history, and successful track record of training early-stage investigators) who have collective research expertise in brain cancer, oncolytic virus, Listeria, tumor angiogenesis, cancer therapeutics, cancer immunology/immunotherapy, and cell signaling. Therefore, with a personalized development plan in place, the mentoring team will provide the necessary career and research guidance to ensure the PI achieves his career goals. Research Applicability: We expect that successful completion of this grant proposal will improve the field of cancer research and patient care by advancing (i) our basic understanding of the immune system’s role in interacting with tumor cells and blood vessels during glioblastoma growth, (ii) the development of novel anti-tumor and anti-blood vessel immunotherapeutic approaches, and (iii) our ability to seek larger grant support for clinical trial funding. Since these studies are in the earliest stages of development, we anticipate to demonstrate translationally relevant results within 2 years that will be clinically adopted for patient treatment within 5-10 years. We expect this new immunotherapeutic strategy will lead to breakthroughs in the ability to safely and effectivel
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010702
Entities
People
- Dipongkor Saha
Organizations
- Texas Tech University Health Sciences Center
- United States Army