Abstract 2048: In vitro and in vivo characterization of non-oncolytic engineered arenavirus vectors for cancer immunotherapy

Abstract

Abstract Cytotoxic CD8+ T cells are paramount for effective cancer immunotherapy. We engineered two distantly related arenaviruses, lymphocytic choriomeningitis virus (LCMV) and Pichinde virus (PICV), encoding the same non-oncogenic HPV16 E7E6 fusion protein to effectively mount and maintain tumor specific CD8+ T cell responses. The designated vectors, HB-201 (LCMV) and HB-202 (PICV), are currently in an ongoing 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 (NCT04180215). To characterize the immunogenic properties of both vectors, we designed a comprehensive set of preclinical and translational experiments utilizing human PBMCs, artificial APCs and HPV16 E6 and E7 specific reporter T cells. This was done in conjunction with a preclinical model for HPV16 associated cancer (TC-1). HB-201 (LCMV) and HB-202 (PICV) surrogate vectors encoding GFP readily infected human monocytes, plasmacytoid dendritic, and conventional dendritic cells. In addition, HB-201 and HB-202 vectors successfully induced antigen presentation of E7 and E6 epitopes as evidenced by TCR reporter cells. Innate immune cell activation and cytokine responses to HB-202 were slightly lower compared to HB-201, findings which are consistent with different memory profiles of E7 specific CD8+ T cells in non-tumor bearing mice. In a therapeutic setting of the TC-1 tumor model, both vectors were comparably effective, showing major infiltration of CD8+ T cells into the tumor microenvironment, tumor growth delay and a significantly prolonged survival already after a single administration. In this data set we have confirmed the strong immunogenicity of the engineered arenavirus platform leading to efficient tumor control in a relevant mouse model for HPV16+ cancers, which further supports the clinical development of our novel arenavirus platform. Citation Format: Josipa Raguz, Theresa Kleissner, Sandra Rosskopf, Mohamed Habbeddine, Katharina Lechner, Valentin Just, Donna Edwards, Igor Matushansky, Christoph Lampert, Klaus K. Orlinger, Henning Lauterbach. In vitro and in vivo characterization of non-oncolytic engineered arenavirus vectors for cancer immunotherapy [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 2048.