Targeting the Immune Landscape of Advanced Bladder Cancer
Abstract
Scientific Objective and Rationale: The militarily relevant focus for this proposal will be Bladder Cancer and Immunotherapy of Bladder Cancer. Bladder cancer is the sixth most common cancer in the United States with over 80,000 newly diagnosed cases expected this year, and it is a common cancer worldwide. Immune checkpoint inhibitors stop the immune system from turning off before the cancer is destroyed. They represent new the treatment paradigms, which in certain instances work better than standard chemotherapy treatment. Unfortunately, the majority of immune checkpoint inhibitors have low efficacies. These immune checkpoint inhibitors are less than 30% effective. One major problem is the lack of knowledge in the immune landscape or microenvironment of bladder tumors as the immune cells can change, depending on the severity of the tumor. As outlined in the Report to Congressional Defense Committees by the Metastatic Cancer Task Force team in April 2018, “One of the largest research gaps in the field of metastasis research is understanding the biological processes that underlie cancer metastasis…” and, “Finally, better experimental models are needed to further study both primary and metastatic Cancer.” The main objective of my proposal is to address an unmet need in defining the immune system of metastatic bladder tumors, and then test the immune landscape by developing a humanized bladder cancer mouse model. This model will develop aggressive bladder tumors, which will be systematically dissected to define the main factors to block or reverse the progression of the cancer. The objective of the first aim of the study will be to identify subpopulations of killer tumor cells as well as immune suppressor cells found in the tumor. As a second portion of this proposal, I will generate a clinically relevant humanized bladder cancer mouse model. My career guide for this award has successfully developed humanized mouse models for other types of cancers, including breast, head and neck, kidney, and colon cancer. Using the tumor and immune cells from a human bladder cancer patient, I will be able to test if priming the immune system will allow the immune system to attack the bladder tumor. The goal of this proposal will be to determine which immune factors are necessary to block or reverse metastatic growth. Principal Investigator’s Career Goals in Cancer Research: This career development award will provide me an important opportunity to gain additional scientific training and mentorship that will enhance my development as an independent cancer researcher. I have extensive training in the drug delivery field for bladder cancer, and now I have an opportunity to gain knowledge in the immunobiology field of bladder cancer. I will focus on the changes in the immune landscape of the tumor and microenvironment, which plays a critical role in the treatment of bladder cancer. As a PhD translational scientist, I am well positioned to be successful on this proposal. My career goal is to synergistically combine my basic science, drug delivery, and clinical research training with my planned immunobiology training proposal to develop novel therapeutics that will benefit all military personnel with advanced bladder cancer. I have assembled a strong mentoring committee, who will provide specific technical and professional aspects of my proposed research and career guidance. This Peer Reviewed Cancer Research Program award will allow me to investigate how the immune microenvironment has the potential to inhibit metastatic bladder cancer progression. The Ultimate Applicability of the Research: This proposal is highly translational, as I will be using human metastatic bladder cancer specimens to evaluate the immune cells’ subpopulations and how the more aggressive tumor types have changes to their immune cells. In addition, my clinically relevant bladder cancer mouse model will directly allow testing of the patient’s tumor with his/her own immun
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010454
Entities
People
- Darryl Martin
Organizations
- United States Army
- Yale University