Abstract 3284: HB-201 and HB-202, an arenavirus-based immunotherapy, induces tumor T cell infiltration in patients with HNSCC and other HPV16+ tumors

Abstract Background: Human Papillomavirus 16 (HPV16) is the most common etiologic agent of HPV-associated cancers. Treatment options are limited for patients with HPV16+ recurrent or metastatic cancers. HPV16 E7 and E6 oncogenes constitute attractive immunotherapeutic targets. HB-201 and HB-202 are live-attenuated replicating vectors based on LCMV and PICV arenaviruses, respectively, that express the same non-oncogenic HPV16 E7E6 fusion protein for induction of tumor specific T cell responses. Methods: A Phase I/II open labelled clinical trial of HB-201 single vector therapy and HB-202/HB-201 alternating two-vector therapy in patients with treatment-refractory HPV16+ cancers is currently ongoing (NCT04180215). To assess circulating E6/E7 specific T cell responses, IFN-γ enzyme-linked immunospot (ELISpot) and intracellular cytokine staining were performed on pre- and post-treatment peripheral blood mononuclear cells (PBMCs). Evaluation of T cell infiltration and PD-L1 status in tumor bed was performed on paired tissue biopsies from a subset of patients by multiplex immunofluorescence. Results: Single vector therapy (HB-201) and alternating two-vector therapy (HB-202/HB-201) rapidly induce high E6/E7 specific T cell levels, reaching up to ~40% of the circulating CD8+ T cell pool. Alternating two-vector therapy seems to maintain E6/E7 specific T cell responses better in continuous dosing compared to single vector therapy. Furthermore, we demonstrate tumor tissue T cell infiltration in more than 50% of patient samples analyzed. Currently, in depth sequencing of paired biopsies is underway to characterize the tumor microenvironment in response to HB-201 and HB-202/HB-201 treatment. Conclusion: In this updated dataset, we show that HB-201 and HB-202/HB-201, rapidly induce unprecedented E6/E7 specific T cell levels in circulation following a single dose. Furthermore, these data are seen in conjunction with a pronounced increase of post-treatment CD8+ T cells in tumor, suggesting E6/E7 specific T cell infiltration. Our arenavirus vectors expressing the E7E6 fusion antigen demonstrate an attractive and safe therapy for patients with treatment refractory HPV16+ cancers. The ability of replicating arenavirus vectors to incorporate a broad range of antigens and the potent T cell inducing capacity provide a strong rationale to apply this novel therapy to other cancers. Citation Format: Donna Edwards, Michael Schwendinger, Kia Katchar, Katia Schlienger, Klaus Orlinger, Igor Matushansky, Henning Lauterbach. HB-201 and HB-202, an arenavirus-based immunotherapy, induces tumor T cell infiltration in patients with HNSCC and other HPV16+ tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3284.