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- Title
DNA Vaccines Targeting Novel Cancer-Associated Antigens Frequently Expressed in Head and Neck Cancer Enhance the Efficacy of Checkpoint Inhibitor.
- Authors
Wang, Chuan; Zainal, Nur Syafinaz; Chai, San Jiun; Dickie, James; Gan, Chai Phei; Zulaziz, Natasha; Lye, Bryan Kit Weng; Sutavani, Ruhcha V.; Ottensmeier, Christian H.; King, Emma V.; Abraham, Mannil Thomas; Ismail, Siti Mazlipah binti; Lau, Shin Hin; Kallarakkal, Thomas George; Mun, Kein Seong; Zain, Rosnah binti; Abdul Rahman, Zainal Ariff; Thomas, Gareth J.; Cheong, Sok Ching; Savelyeva, Natalia
- Abstract
HPV-independent head and neck squamous cell carcinoma (HNSCC) is a common cancer globally. The overall response rate to anti-PD1 checkpoint inhibitors (CPIs) in HNSCC is ~16%. One major factor influencing the effectiveness of CPI is the level of tumor infiltrating T cells (TILs). Converting TILlow tumors to TILhigh tumors is thus critical to improve clinical outcome. Here we describe a novel DNA vaccines to facilitate the T-cell infiltration and control tumor growth. We evaluated the expression of target antigens and their respective immunogenicity in HNSCC patients. The efficacy of DNA vaccines targeting two novel antigens were evaluated with or without CPI using a syngeneic model. Most HNSCC patients (43/44) co-expressed MAGED4B and FJX1 and their respective tetramer-specific T cells were in the range of 0.06-0.12%. In a preclinical model, antigen-specific T cells were induced by DNA vaccines and increased T cell infiltration into the tumor, but not MDSC or regulatory T cells. The vaccines inhibited tumor growth and improved the outcome alone and upon combination with anti-PD1 and resulted in tumor clearance in approximately 75% of mice. Pre-existence of MAGED4B and FJX1-reactive T cells in HNSCC patients suggests that these widely expressed antigens are highly immunogenic and could be further expanded by vaccination. The DNA vaccines targeting these antigens induced robust T cell responses and with the anti-PD1 antibody conferring excellent tumor control. This opens up an opportunity for combination immunotherapy that might benefit a wider population of HNSCC patients in an antigen-specific manner.
- Subjects
ANTIGENS; DNA vaccines; REGULATORY T cells; HEAD &; neck cancer; T cells; TUMOR growth
- Publication
Frontiers in Immunology, 2021, Vol 12, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2021.763086