Identification of Immunogenic Targets for Lung Cancer Vaccines
Abstract
Scientific Objective and Rationale: The aim of this project is to develop a vaccine for lung cancer prevention that can stimulate the immune system to specifically eradicate the abnormal lung cancer cells. This project addresses the Lung Cancer Research Program Area of Emphasis: "Identify innovative strategies for prevention and treatment of early and/or localized lung cancer." Lung cancer is the leading cause of death from cancer. It is highly smoking-related (85% of cases arise in smokers); however, smoking cessation does not decrease the risk of cancer. Once diagnosed, current treatments, surgery and/or chemotherapy, are not effective, and more than 70% of patients die within a year after diagnosis. Vaccines that boost the immune system in order to target and destroy the tumor cells can prevent the development of cancer. Cancer vaccine efficacy has been proven for prostate cancer, liver cancer, and cervical cancer. Contrary to what was believed, recent data have shown that there is also immune response against lung cancer. This project applies our most recent discoveries of how the immune system functions and interacts with abnormal pre-cancer cells to design a novel approach to prevent lung cancer prior to diagnosis. Cancer vaccines can be formulated using antigens (proteins recognized by the immune system) that are associated with lung cancer. Studies in breast cancer have shown that proteins with increased expression on cancer cells can stimulate an immune response. In order for a cancer vaccine to be effective, generation of a strong inflammatory response is needed. This is called "Type I immunity" (or Th1), where inflammatory factors called cytokines are released by a type of white blood cell called T cells, launching an attack against tumors. This acute inflammatory response can recruit other types of immune cells in the body to the tumor, and it can also help the body generate memory to mount a response against these atypical proteins for the future. A brisk Th1 response is needed to successfully kill cancer cells and thereby eradicate tumors. Data from our group have shown that regions exist within these tumor antigens that are more likely to stimulate the Th1 immune response. A vaccine stimulating an acute inflammatory response to recognize and attack upregulated antigens associated with lung cancer may allow elimination of lung cancer. In this project, we will identify candidate proteins that are overexpressed in lung cancer cell lines that play a role in the abnormal cell survival. We will study the effect of inhibiting the expression of those proteins on cell survival and cell death in human lung cancer cell lines in order to select as targets those proteins that favor cell survival and decrease cell death. We will then use web-based computer programs to predict which portions of these proteins are most likely to be recognized by the immune system in the majority of the population. We will study which of those areas of the proteins stimulate the strongest Th1 response when exposed to human T cells, with plans to select these portions of the proteins to use in vaccine formulation. We will use ELISPOT immune tests in early lung cancer patients blood to select antigens that will produce a brisk Th1 response. Before testing the vaccine in humans, it will be important to ensure efficacy in a mouse model that mimics lung cancer. We will construct a multi-antigen vaccine and determine if the vaccine is immunogenic, safe, and effective in preventing lung cancer in mouse models. Principal Investigator s Goals in Lung Cancer Research: My goal is to become an independent translational faculty member developing novel immune-based therapies for patients with lung cancer. This proposal includes not only a novel vaccine development strategy, but also a comprehensive training plan to ensure my success as a young investigator in the field of lung cancer immunotherapy. The combination of exper
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610107
Entities
People
- Laura Riolobos
Organizations
- United States Army
- University of Washington