Head & neck squamous cell carcinoma (HNSCC) is currently showing clinical response to immune checkpoint inhibitors, but its efficacy is still low at nearly 20% of the recurrent/metastatic patients treated. One immunological strategy to improve upon this low efficacy rate is to target the high mutational burden of HNSCC, particularly those associated with chronic tobacco exposure. We propose to characterize the mutation associated neoantigen landscape of human HNSCC obtained from patients treated with nivolumab in a neoadjuvant setting using both in silico and mass spectroscopy methods to directly obtain these human neo- epitopes. In conjunction with these studies, we will characterize the immunodominant MHC restricted neoantigens in an autologous humanized murine system in vivo. These findings will help direct a novel strategy to expand these neoantigen-specific T-cells using a potent STING agonist formulated nanoparticles with known neoantigens found in human HNSCC. Findings from this proposal will also impact how neoantigen-based cancer vaccines should be administered in conjunction with immune checkpoint inhibitors in future head and neck clinical trials. Lastly, our proposal will also inform neoepitope prediction algorithms and antigen based trials for other cancer types to have deep impact in the field of cancer immunology as a whole.

Public Health Relevance

In concordance with the mission statement of NIH and NIDCR, this proposal seeks to characterize the neoantigen landscape in head and neck cancer patients. Based on these findings, we will develop novel neoantigen based cancer vaccines for head and neck cancer patients for the purpose of enhancing the health of oral, oropharyngeal, and laryngeal cancer patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE027749-03
Application #
9967822
Study Section
Special Emphasis Panel (ZDE1)
Program Officer
Wang, Chiayeng
Project Start
2018-07-01
Project End
2023-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
079917897
City
Nashville
State
TN
Country
United States
Zip Code
37232