Survivin-targeted immunotherapy drives robust polyfunctional T cell generation and differentiation in advanced ovarian cancer patients.
Journal Article (Journal Article)
DepoVax™ is an innovative and strongly immunogenic vaccine platform. Survivin is highly expressed in many tumor types and has reported prognostic value. To generate tumor-specific immune response, a novel cancer vaccine was formulated in DepoVax platform (DPX-Survivac) using survivin HLA class I peptides. Safety and immune potency of DPX-Survivac was tested in combination with immune-modulator metronomic cyclophosphamide in ovarian cancer patients. All the patients receiving the therapy produced antigen-specific immune responses; higher dose vaccine and cyclophosphamide treatment generating significantly higher magnitude responses. Strong T cell responses were associated with differentiation of naïve T cells into central/effector memory (CM/EM) and late differentiated (LD) polyfunctional antigen-specific CD4+ and CD8+ T cells. This approach enabled rapid de novo activation/expansion of vaccine antigen-specific CD8+ T cells and provided a strong rationale for further testing to determine clinical benefits associated with this immune activation. These data represent vaccine-induced T cell activation in a clinical setting to a self-tumor antigen previously described only in animal models.
Full Text
Duke Authors
Cited Authors
- Berinstein, NL; Karkada, M; Oza, AM; Odunsi, K; Villella, JA; Nemunaitis, JJ; Morse, MA; Pejovic, T; Bentley, J; Buyse, M; Nigam, R; Weir, GM; MacDonald, LD; Quinton, T; Rajagopalan, R; Sharp, K; Penwell, A; Sammatur, L; Burzykowski, T; Stanford, MM; Mansour, M
Published Date
- August 2015
Published In
Volume / Issue
- 4 / 8
Start / End Page
- e1026529 -
PubMed ID
- 26405584
Pubmed Central ID
- PMC4570133
International Standard Serial Number (ISSN)
- 2162-4011
Digital Object Identifier (DOI)
- 10.1080/2162402X.2015.1026529
Language
- eng
Conference Location
- United States