Abstract 1460: Generation of a novel, allogeneic cell-based, Gp96-Ig/OX40L cancer vaccine, improves anti-tumor immunity and long-term memory T-cell generation

Abstract

Abstract Our technology is focused on developing a next generation cellular vaccine platform – referred to as ComPACT (COMbination Pan-Antigen Cytotoxic Therapy), that incorporates a tumor antigen chaperone (gp96-Ig) with T-cell costimulation (OX40L-Ig), into a single tumor cell line that secretes both. Viagenpumatucel-L (HS-110; ImPACT), a human lung adenocarcinoma cell line, stably transfected to express gp96-Ig is being tested in a phase 1/2 clinical trial (NCT#02439450) with checkpoint inhibition for NSCLC. A similar line is being generated that will complement HS-110, providing costimulation in the form of secreted OX40-Ig (HS-130). To model how the addition of human HS-130 to HS-110 may impact anti-tumor immune responses, we generated mouse surrogates of these human lines and established an analogous system, that treats tumor-bearing animals with tissue-matched irradiated cancer cell lines (B16F10) expressing gp96-Ig (mHS-110) and OX40L-Ig (mHS-130) both expressing ovalbumin, as our model tumor-associated antigen. Single dose vaccination with mHS-110 identified that 1 to 10 million cells (290 ng to 2,900 ng of secreted gp96-Ig) provided sufficient anti-tumor CD8+ T-cell expansion, in vivo (*p<0.01; 1-way ANOVA), with the greatest expansion observed on day 7, post-immunization. To identify the best ratio of mHS-110 to mHS-130; a dose ratio study was performed. Fixed numbers of mHS-110 (1 million cells, 290 ng of secreted gp96-Ig) were matched with different ratios of mHS-130. Similar to our single dose vaccination study, our results demonstrated that the peak CD8+ T-cell expansion occurred on day 7 post-immunization, and that the addition of mHS-130 further boosted anti-tumor CD8+ T-cell expansion by 3-fold when the ratios of mHS-110 to mHS-130 were at a 1-to-1 ratio (290 ng of secreted gp96-Ig to 290 ng of secreted OX40L-Ig) (*p<0.05, Mann-Whitney). These animals were subsequently boosted 14-days post-immunization, and we similarly found that the 1-to-1 ratio of mHS-110 to mHS-130 gave the maximum expansion of CD8+ T cell responses, peaking on day 21 and contracting thereafter (*p<0.05; Mann-Whitney). Importantly, these ratios led to high frequencies of IFNγ+ antigen-specific CD8+ T cells at both priming and boosting, which enhanced rejection of established B16F10 tumors and increased overall survival. Citation Format: Vikas Tahiliani, Jayalakshmi Miriyala, Patrick Dillon, Jason Rose, Louise Giffin, Jeff Hutchins, Matthew M. Seavey. Generation of a novel, allogeneic cell-based, Gp96-Ig/OX40L cancer vaccine, improves anti-tumor immunity and long-term memory T-cell generation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1460.