Enhanced Melanoma Vaccine Against Neoantigens and Shared Antigens by CD40 Activation and TLR Agonists
Abstract
FY18 PRCRP Topic Area(s): This proposal is submitted in response to the FY18 Peer Reviewed Cancer Research Program and addresses the “melanoma and other skin cancers” and “Immunotherapy” topic areas. Scientific objective and rationale: Melanoma is a common cancer that can spread throughout the body, and it is responsible for deaths of about 10,000 Americans annually. It has recently become clear that immune responses to melanoma can control its development and that enhancing those immune responses can be therapeutic. Most effective immunotherapies now carry risks of severe side effects caused by unregulated immune activation. Cancer vaccines have long held promise by inducing specific immune responses to melanoma with little risk of major side effects on normal tissues. However, the promise of melanoma vaccines has not yet been realized. The present application is for a project to test new approaches to melanoma vaccines that promise to induce strong and effective immune responses and to offer the potential for use in melanoma prevention by targeting a common mutation in nevi (moles) that can lead to melanoma. Ultimate applicability of the research: This project includes a clinical trial that will enroll melanoma patients at two institutions and that will test safety and immune response to the vaccines, while also characterizing molecular and cellular aspects of the immune response in skin (vaccine sites and nevi) and in blood and lymph nodes. These studies will enhance our understanding of how to enhance melanoma vaccines specifically, and cancer vaccines, broadly. If the approaches tested here are effective, they will support a future randomized prospective trial in melanoma therapy as well as further development of vaccines for control of atypical nevi and for melanoma prevention. Military Relevance: This proposal addresses the FY18 PRCRP Military Relevance Focus Areas “Militarily relevant risk factors associated with cancer (e.g., ionizing radiation, chemicals, infectious agents, environmental carcinogens, and stress),” and “gaps in cancer prevention, early detection/diagnosis, prognosis, treatment and/or survivorship that may impact mission readiness and the health and well-being of military members, Veterans, their beneficiaries, and the general public.” This project will address current needs in treatment and prevention of melanoma that may aid in prolonging life and reducing morbidity for active and retired military. If this vaccine approach is effective, it will pave the way for further development of this approach which may prevent melanomas and enhance dramatically the quality of life of melanoma patients. All of these benefits would enhance mission readiness of active military and their families by avoiding melanoma and/or treating it with low treatment toxicity. The patients to be studied in this project will be of a comparable age range and health status of active and retired military. Conceivably, some of these patients may actually be in the national guard, active military, reserve status, or retired military. Regardless, the patient population will be very representative of the military population so that lessons learned here will be applicable to active military, their families, and U.S. veterans.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- W81XWH1910338
Entities
People
- Craig Slingluff
Organizations
- United States Army
- University of Virginia