Vaccines targeting novel cancer-associated antigens frequently expressed in head and neck cancer enhance the efficacy of checkpoint inhibitor

Wang, Chuan and Zainal, Nur Syafinaz and Chai, San Jiun and Dickie, James and Gan, Chai Phei and Zulaziz, Natasha and Lye, Bryan Kit Weng and Sutavani, Ruhcha and Ottensmeier, Christian H. and King, Emma and Abraham, Mannil Thomas and Ismail, Siti Mazlipah and Lau, Shin Hin and Kallarakkal, Thomas George and Mun, Kein Seong and Zain, Rosnah and Rahman, Zainal Ariff Abdul and Thomas, Gareth J. and Cheong, Sok Ching and Savelyeva, Natalia and Lim, Kue Peng (2021) Vaccines targeting novel cancer-associated antigens frequently expressed in head and neck cancer enhance the efficacy of checkpoint inhibitor. Frontiers in Immunology, 12. ISSN 1664-3224, DOI

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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 similar to 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.

Item Type: Article
Funders: Ungku Omar Fund and the Medical Research Council UK Newton fund [MR/PO13414/1], Cancer Research Malaysia
Uncontrolled Keywords: DNA vaccine; Cancer immunotherapy; Head and neck cancer; MAGED4B; FJX1; Cancer antigens
Subjects: Q Science > QR Microbiology > QR180 Immunology
Divisions: Faculty of Dentistry > Dept of Oral & Maxillofacial Surgery
Faculty of Medicine > Pathology Department
Depositing User: Ms Zaharah Ramly
Date Deposited: 10 Aug 2022 02:54
Last Modified: 10 Aug 2022 02:55

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