PO-516 E6/E7 RNA(LIP): a novel liposomal RNA vaccine for treatment of patients with HPV16-positive malignancies

Abstract

Introduction Human papillomavirus (HPV) has emerged as a major risk factor for Head Neck squamous cell carcinoma (HNSCC) and the incidence of HPV-positive HNSCC continues to rise. Standard treatment of HNSCC given with curative intent causes substantial and long-term physical and functional impairments, but nonetheless, approx. 50% of patients die of their disease. Alternative treatments are urgently needed to improve survival but also to reduce treatment-associated morbidity. Both CD8+ and CD4+ T cells are important for viral clearance and regression of HPV-positive premalignant lesions; density of tumor-infiltrating lymphocytes (TILs) is a strong predictor of the outcome of HPV-positive oropharyngeal cancers. Consequently, therapeutic cancer vaccines hold great promise to achieve longterm disease control in HPV-positive malignancies if they generate tumour antigen-specific and durable anti-cancer immunity that can recognise viral antigen at the tumour site. Material and methods Recent advances in the systemic delivery of antigen-encoding lipid-complexed RNA (RNA(LIP)) allow efficient targeting and RNA delivery to secondary lymphoid organs body-wide with early data supporting substantial immunological and clinical effects. With E6/E7 RNA(LIP), BioNTech has developed a promising immunotherapeutic approach to address a high unmet medical need. Results and discussions E6/E7 RNA(LIP) is the first systemically administrable therapeutic cancer vaccine based on two lipidcomplexed RNA drug products targeting the well-characterised HPV16-derived viral antigens E6 and E7. Preclinical studies in two independent syngeneic mouse tumour models demonstrated that vaccine treatment significantly increased the frequency of TILs, leading to strong tumour microenvironment polarisation and consistent regression of large established tumours. Conclusion Based on the encouraging preclinical proof-of-concept data, E6/E7 RNA(LIP) is currently evaluated in a multicentre, first-in-human phase I/II trial in patients with HPV16- positive HNSCC and other HPV16-positive cancers (Sponsor: University Hospital of Southampton NHS Foundation Trust; Eudra CT No.: 2014-002061-30). Objectives of the trial are to study safety, tolerability, and immunogenicity of the novel immunotherapeutic approach. Where measurable tumour is present clinical response rate and expansion of HPV-specific TILs will be evaluated. Here we present the preclinical proofof- concept data as well as preliminary data from the ongoing clinical trial.