Efficacy of Combination of Immunotherapies in a Murine in a Murine Squamous Cell Carcinoma Model

Introduction: Head and neck squamous cell carcinomas (HNSCCs) are a type of neoplasm found in the epithelium of the oral cavity, oropharynx, nasopharynx, larynx, or hypopharynx. Recent evidence has demonstrated that 70-90% of HNSCC are associated with Human Papillomavirus (HPV), particularly strain 16 producing oncogenic proteins E6/E7. Currently, HNSCCs are treated with surgery, chemotherapy, and radiation, however immunotherapy with immune checkpoint (PD-1) blocking agents promises to improve outcomes in HNSCC. Objective: This study examined the therapeutic effects of dual and triple combination immunotherapies in a mouse model of HPV-associated HNSCC. Methods: Treatment modalities included a tumor vaccine (attenuated Listeria monocytogenes based vaccine encoding HPV16 E6/E7 (AXAL)), an immune checkpoint inhibitor targeting PD1 (RMP1-14) and topical subtherapeutic radiation. Mice were injected subcutaneously with tumor cells expressing HPV16 E6/E7 (TC-1). When tumors were established, mice were vaccinated with AXAL (3 injections) either alone and/or with anti-PDi and/or with a single dose of radiation. Results: Partial responses were observed in some mice receiving dual combination therapies. Most mice treated with triple immunotherapy revealed complete tumor regression. Discussion: Combination immunotherapy is effective in the TC-1 HNSCC model system. The results obtained set the stage for investing immune mechanism underpinning treatment-associated tumor regression