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Oncoimmunology. 2015 May 7;4(8):e1026529. eCollection 2015 Aug.

Survivin-targeted immunotherapy drives robust polyfunctional T cell generation and differentiation in advanced ovarian cancer patients.

Author information

1
Sunnybrook Health Sciences Centre ; Toronto, Ontario, Canada.
2
Immunovaccine, Inc. ; Halifax, Nova Scotia, Canada.
3
Princess Margaret Cancer Center; University Health Network ; Toronto, Ontario, Canada.
4
Roswell Park Cancer Institute ; Buffalo, NY USA.
5
Winthrop-University Hospital ; Mineola, NY USA.
6
Mary Crowley Cancer Research Center ; Dallas, TX USA.
7
Duke University Medical Center ; Durham, NC USA.
8
Oregon Health & Science University ; Portland, OR USA.
9
QEII Health Sciences Center ; Halifax, Nova Scotia, Canada.
10
International Drug Development Institute (IDDI) ; Louvain la Neuve, Belgium.

Abstract

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.

KEYWORDS:

DepoVax; T cells; cancer; immunotherapy; survivin

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