High-Throughput TCR Repertoire-Based Platforms for Antigen-Specific Cancer Immunotherapy
Abstract
We seek to develop new platform technologies that will help us to better understand why and how immune-based cancer treatments are effective and to apply that fundamental knowledge to develop rapid, targeted cancer therapeutics and improve cancer care. Modern immune-based therapies have shown tremendous success for treating many different kinds of cancers, and T cells play a critical role in these treatments because they have a unique ability to specifically target and selectively destroy tumor cells. However, T cells are difficult to analyze in the laboratory because each T cell has multiple unique genes, and thus each T cell must be studied one cell at a time. This study will overcome these barriers and develop new ways to analyze T cell responses for millions of cells at once, allowing us to understand anti-cancer T cell responses at a much broader scale than is currently possible. We will apply these technologies to understand the mechanistic features of cancer-specific T cell targeting and apply that information to develop more precise and effective cancer therapeutics. This project will provide a major boost to Dr. DeKosky’s research career, which will focus on identifying the mechanisms of how immunotherapy effectively fight cancer, and also in developing new drugs for improved cancer treatments that specifically target cancer cells while sparing other body tissues. Once these initial projects have been established, they will be expanded to better understand T cell responses in cancer patients and to identify the molecular targets of cancer-killing T cells. Thus, the technologies developed by this project will both broaden our knowledge of anti-tumor responses and accelerate discovery of new cancer treatments. This research is a direct precursor to developing new, targeted immune-based therapies that can selectively destroy cancer cells, and it will be useful for many patient types but especially for patients whose cancers are a result of environmental exposure risks (e.g., lung cancer, melanoma, etc.), both for solid tumors and for distributed cancers. The highly specific nature of these treatments will generate more effective cancer cell killing while also reducing off-target side effects, resulting in streamlined, personalized cancer treatments that are customized for each unique patient. Methods and techniques in immunotherapy are rapidly developing, and clinical trials could begin with these new treatment platforms in 5-7 years. Military populations show enhanced risk of several cancer types, including melanoma, lung cancer, and others that can result from environmental changes caused by radiation, sun exposure, and chemical exposure during and after military service. While the cancer-specific treatments developed through this research will be beneficial for many non-military patients, these new drug technologies will have an outsized benefit for the care and treatment of military Service members and Veterans because many cancers that these treatments will be most highly effective against (e.g., which are strongly associated with environmental risk factors) are more prevalent in individuals who have performed military service.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810296
Entities
People
- Brandon J DeKosky
Organizations
- United States Army
- University of Kansas