P-06.01 Survivin-based vaccine induces durable tumor regression when integrated with specific sequential antiangiogenic and immune checkpoint therapies

<h3>Background</h3> While <b>peptide-based vaccines</b> have shown the ability to induce antitumor immune responses, their clinical application as standalone therapies has largely been hindered by <b>limited efficacy</b>, particularly in highly immunosuppressive solid tumors. Our team previously demonstrated that the survivin-based peptide vaccine achieves <b>better tumor growth control when administered following antiangiogenic therapy</b>, emphasizing the importance of optimized treatment schedules.^{1 2} Building on these findings, we investigated the integration of this vaccine into a <b>tritherapy</b> combining Axitinib, a more potent anti-angiogenic agent, and <b>anti-PD1</b> therapy—an approach already used in clinical practice. This study focused on a precisely timed administration strategy in an orthotopic renal carcinoma model, aiming to understand the underlying mechanisms, including immune response and tumor microenvironment modulation. <h3>Materials and Methods</h3> We established an orthotopic <b>renal cancer model</b> (RENCA-luc+ cells in Balb C mice). Tumor growth was monitored using <b>bioluminescence imaging</b>. A novel schedule was implemented, administering Axitinib first, followed by the peptide-based vaccine and anti-PD1 (CD279). The tumor microenvironment (TME) was analyzed using multiplex immunofluorescence, while immune populations were studied by flow cytometry, functionality through luminex assay, and cytotoxic assay in vitro. <h3>Results</h3> Administering Axitinib first normalized tumor vasculature and reduced hypoxia, followed by the survivin vaccine and anti-PD1. This sequential strategy resulted in <b>70% tumor regression</b> and durable growth control, as monitored by bioluminescence imaging, compared to Axitinib alone or Axitinib+anti-PD1. Tritherapy demonstrated a clear synergy, significantly surpassing monotherapies and double combinations in tumor suppression. Multiplex immunofluorescence showed substantial <b>vascular normalization</b> and reduced hypoxia, favoring <b>enhanced immune infiltration</b>. The combination increased intratumoral CD8+ T cells, CD4+ T cells, B cells, and NK cells. Notably, <b>CD8+ T cells exhibited heightened functionality</b> with increased secretion of key effector cytokines, including granzyme B, IFNγ, and IL-2. <h3>Conclusions</h3> This study demonstrates that the survivin peptide vaccine, when precisely integrated with Axitinib and anti-PD1, achieves a <b>clear synergy</b> on profound tumor regression and durable immune responses in an orthotopic renal carcinoma model. Tritherapy significantly outperforms monotherapies and double combinations in tumor control. These findings underscore the critical role of treatment sequencing and position the vaccine as a cornerstone for innovative combinatorial cancer therapies. <h3>References</h3> Onodi F, <i>et al. Frontier in Oncology</i> 2018. Mougel A, Méjean F, <i>et al. Oncoimmunology</i> 2022. F.M. Méjean: None.