Exploiting the Immunosurveillance Function of CD137 Immune Checkpoint for Lung Cancer Prevention
Abstract
The major objective of this proposal is to assess the ability of a novel immune checkpoint booster, SA-4-1BBL, as a single agent to train the immune system to prevent lung cancer development in a preclinical animal model relevant to high-risk individuals, such as tobacco smokers. Thus, this proposal addresses “identify innovative strategies for prevention of the occurrence of lung cancer” as one of the Areas of Emphasis for FY 19 LCRP Concept Award. Lung cancer is the most common cause of cancer-related death in Service members, Veterans, beneficiaries, and the general public. Regardless of significant improvement over the years, standard treatment regimens not only have severe toxicity, but also fail to control lung cancer in most patients, particularly those with advanced disease. Therefore, the development of new, more effective therapies with no or minimal toxicity is of significant interest and represents a critical unmet medical need. Several Food and Drug Administration-approved cancer immune-based therapies have validated the long-standing notion that the immune system is a critical defense mechanism against cancer. Now that the immune system as an important target to treat cancer has been clinically validated, immunoprevention becomes the next frontier to combat cancer. We hypothesize that the immune system has a surveillance mechanism that eliminates arising tumor cells before cancer develops. In this application, we will test this hypothesis using SA-4-1BBL to enhance this naturally occurring surveillance mechanism in an animal model of lung cancer induced by a tobacco carcinogen. If successful in the proposed preclinical model, SA-4-1BBL will represent not only a transformative immunomodulatory concept, but also a practical and cost-effective approach for the prevention of lung cancer in high-risk individuals and potentially control of recurrence following first-line treatments such as surgery or chemo/radiotherapy. Importantly, this immunotherapy platform can be applied to a variety of other cancer types, in particular, breast and prostate cancers, for which better diagnostics can detect cancer at the preneoplastic stage. The military population may be more prone to lung cancer than the general public because of the higher likelihood of smoking and smoking more heavily. They also have a higher likelihood of exposure to cancer-causing agents during their Service that may translate into a higher incidence of lung cancer in Veterans. Therefore, if successful, SA-4-1BBL will help, not only active military Service members and Veterans, but also their families and the general public with significant health and economic benefits. Given the intense recent interest by the industry for the development of safe and effective immunotherapies, the demonstrated efficacy of SA-4-1BBL in the proposed tobacco-induced lung cancer preclinical animal model will help its rapid development and translation of this concept to the clinic for the prevention and recurrence of lung cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010459
Entities
People
- Esma Yolcu
Organizations
- Curators of the University of Missouri
- United States Army