Affiliations 

  • 1 Head and Neck Cancer Center, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United Kingdom
  • 2 Cancer Immunology and Immunotherapy Unit, Cancer Research Malaysia, Selangor, Malaysia
  • 3 Cancer Sciences, University of Southampton, Southampton, United Kingdom
  • 4 Ministry of Health Malaysia, Department of Oral & Maxillofacial Surgery, Tengku Ampuan Rahimah Hospital, Klang, Malaysia
  • 5 Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia
  • 6 Stomatology Unit, Cancer Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia
  • 7 Department of Pathology, Faculty of Medicine, University of Malaya, Selangor, Malaysia
  • 8 Oral Cancer Research and Coordinating Centre, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia
  • 9 Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University Teknologi Majlis Amanah Rakyat (MARA), Selangor, Malaysia
Front Immunol, 2021;12:763086.
PMID: 34733290 DOI: 10.3389/fimmu.2021.763086

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.