Abstract LB117: Virus-inspired Particles (ViPs) harnessing cytomegalovirus immune memory for local and systemic cancer immunotherapy

Abstract VerImmune is pioneering a First-in-Class treatment known as “Anti-tumor Immune Redirection” (AIR). This approach repurposes a patient’s pre-existing anti-viral or childhood vaccine immunity towards tumor cells for targeted destruction. VerImmune’s lead product, VERI-101, leverages pre-existing CD8+ T-cell immune memory acquired from past human cytomegalovirus (HCMV) infections. VERI-101 consists of VerImmune’s proprietary platform technology known as ViPs (Virus-inspired Particles) that are conjugated on their surface with a CD8+ T cell viral peptide antigen. ViPs are based on a modified mouse papillomavirus capsid protein of which 60 copies self-assemble into a 20-30nm T=1 icosahedral structure. In the case of VERI-101, the ViP is conjugated with an HLA-A*0201 restricted peptide epitope (NLVPMVATV, [NLV]), derived from the CMV pp65 antigen with an upstream furin protease cleavage site. The mechanism of action of AIR-ViPs including VERI-101 has been previously presented and involves three steps. Briefly, (1) VERI-101 targets the surface of the tumor cells and (2) enables the presentation of the CMV viral epitopes on their surface MHC, together (3) stimulating a recall of the pre-existing CMV memory response to attack the cancer cells (Dorrier et al., 2023 AACR). Here, we sought to study the in vivo anti-tumor efficacy of AIR-ViPs via both intra-tumoral and systemic treatment routes in two murine tumor models with pre-existing murine CMV (MCMV) immunity: (1) MC38 subcutaneous tumors for local and (2) B16.F10 lung metastasis for systemic treatments. As human CMV is species-specific, instead of VERI-101, a surrogate product, VERI-003 which redirects MCMV immunity, was tested as a single agent or in combination with anti-PD-1 in these tumor models. Our intra-tumoral studies with VERI-003 alone showed a dose-dependent anti-tumor effect (from 5 to 100ug) compared to no treatment controls. Surprisingly, no dose dependence was observed across the same three dose levels when combined with anti-PD-1, although significantly better anti-tumor effects occurred leading to complete tumor clearances in 50% of mice. Statistically significant prolonged survival was observed in most treated groups compared to controls. Our systemic studies with VERI-003 were consistent with our intratumoral studies in showing statistically significant single agent anti-tumor efficacy against B16.F10 lung metastases compared to no treatment. Anti-tumor effects of anti-PD-1 and combination were also observed. Additional studies are on-going to assess dose dependence and analysis of PK/PD effects. Taken together, our initial in vivo results demonstrate the tumor antigen-agnostic therapeutic potential of AIR and our AIR-ViP technology as a novel class of immuno-therapeutic drugs that could be used either as a monotherapy or in combination with checkpoint inhibitors. Citation Format: Cayce Dorrier, Felagot Abebe, Olivia Pak, Emily De-Bodene, Joshua Wang. Virus-inspired Particles (ViPs) harnessing cytomegalovirus immune memory for local and systemic cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB117.