IL-17-Polarizing Vaccination Targeting MUC1 for the Prevention of Lung Cancer
Abstract
Lung cancer is the leading cause of cancer-related mortality in U.S. Veterans, resulting in more deaths than colon, prostate, and breast cancers combined. Significantly, the burden of lung cancer among Veterans is nearly double that of the general population. Under the right conditions, the body?s immune system is able to recognize and destroy the cancerous cells that form tumors. Although vaccines that boost immunity have proven effective at preventing cervical cancer and infectious diseases, no vaccine to date has been able to prevent lung cancer. In our work, we seek to apply innovative technologies and modern understanding of the immune response against tumors to generate a new class of intervention, an effective vaccine capable of preventing lung cancer. Our vaccine boosts immunity against a protein called MUC1, which is present on over 80% of all lung cancers, but is not found on normal healthy cells. Targeting MUC1 has proven to be safe, and lung cancer patients who naturally developed immunity against MUC1 have increased survival. Unlike conventional vaccines, our new vaccine generates a unique, highly specialized type of immune cell, termed T cells, capable of producing the inflammatory factor Interleukin-17 to destroy tumors. To determine if the vaccine is effective, we will test the ability of the vaccine to prevent lung tumors from forming in mice challenged with lung cancer cells that contain the human MUC1 target. In addition, we will test the vaccine in combination with a new immune-enhancing drug that eliminates suppressive cells in the body, thus further strengthening the immune response against the tumor cells. To characterize the immune cells generated by the vaccination, we will employ a new technology capable of determining every activated gene within a single cell. Comparing the function of immune cells that are able to destroy tumors with the function of those that are not effective will allow us to identify a signature of an immune response capable of preventing lung cancer. This immune signature could be used to predict which patients are protected from and which may be at higher risk of lung cancer in the future. Thus, our study addresses two areas of emphasis of the Lung Cancer Research Program: to create an innovative strategy to prevent lung cancer and to define predictive markers to identify responders or non-responders receiving immune-based treatments. If successful, the proposed study would establish the proof necessary to advance the vaccine to clinical trials to protect people. Although protection of high-risk populations such as military Service personnel and Veterans must be prioritized, the novel vaccination strategy we propose could be used to protect the general public as well. As the American Cancer Society estimates that approximately 224,000 new lung cancer cases were diagnosed in 2016, a successful intervention to prevent the ~80% of MUC1-expressing tumors would result in a reduction of roughly 179,000 cases of lung cancer nationally per year. Given the limitation of our current treatments, development of alternative interventions to prevent lung cancer is essential to address the unmet needs of military Service members, Veterans, and the American public.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710189
Entities
People
- Adam C Soloff
Organizations
- Medical University of South Carolina
- United States Army