Abstract CT411: Immune profiling of patients vaccinated with the survivin targeted therapeutic vaccine DPX-Survivac demonstrates durable polyfunctional CD4+ and CD8+ T cells in ovarian cancer patients

Abstract

Survivin is a member of the inhibitor of apoptosis protein family and its over-expression has been reported in many cancer types such as melanoma, colon, brain, breast, and ovarian cancers making it a promising target for immunotherapy. DPX-Survivac is a Survivin multi-epitope vaccine that covers a broad range of HLA haplotypes (HLA-A1, A2, A3, A24, B7). The adjuvanted water free depot vaccine is designed to specifically induce CD8+ T cells. In a Phase I study in ovarian cancer patients (n=18), we aimed to evaluate one dose level of the vaccine (0.5 mL) without cyclophosphamide (Cohort A) and two dose levels (0.1 mL and 0.5 mL) combined with oral low dose cyclophosphamide as an immune modulator (Cohorts B and C). Using multiparametric flow cytometry, we measured the ex-vivo frequency, phenotype and function of Regulatory T cells (CD25+FoxP3+Ki67+) and Survivin-specific CD4 and CD8 T cells. Our data shows that cohort C preferentially mounted survivin-specific CD8 T cells which significantly peaked at one month following the third vaccination (study day 70) and persisted until at least day 126 post-vaccination. This polyfunctional T cell response was endowed with cytotoxic and proliferative functions as measured by the expression of IL-2, IFNγ, TNFα, Granzyme B and CD107a. The immune responses identified in this cohort functionally diversified over time and were distributed within the Effector memory (CD45RA-CD27-), Central Memory (CD45RA-CD27+) and Late Differentiated CD8 T cell pool (CD45RA+CD27-). Of note, polyfunctional CD4 helper responses directed against tetanus toxoid and Survivin were induced by DPX-Survivac and possibly contributed to the maintenance of the CD8 T cell response. Taken together, the data presented herein shows that DPX-Survivac induced durable polyfunctional CD4 helper and CD8 T cells providing a strong rationale for combining the targeted immune therapy with immune modulation using metronomic cyclophosphamide. Citation Format: Yoav Peretz, Dominike Sauvé, Dominic Gagnon, Salim Ahmed Khan, Geneviève Lévesque, Nathalie Saha, Gilbert Croteau, Valérie Hébert, Karyne Savard, Bader Yassine Diab, Jean-Francois Poulin, Claire Landry, Mohan Karkada, Marc Mansour. Immune profiling of patients vaccinated with the survivin targeted therapeutic vaccine DPX-Survivac demonstrates durable polyfunctional CD4+ and CD8+ T cells in ovarian cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT411. doi:10.1158/1538-7445.AM2014-CT411