title: Survivin-targeted immunotherapy drives robust polyfunctional T cell generation and differentiation in advanced ovarian cancer patients.
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 rapidde novoactivation/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.
authors.affiliation: Sunnybrook Health Sciences Centre ; Toronto, Ontario, Canada.
authors.forename: Neil L
authors.initials: NL
authors.lastname: Berinstein
authors.affiliation: Immunovaccine, Inc. ; Halifax, Nova Scotia, Canada.
authors.forename: Mohan
authors.initials: M
authors.lastname: Karkada
authors.affiliation: Princess Margaret Cancer Center; University Health Network ; Toronto, Ontario, Canada.
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
authors.affiliation: Roswell Park Cancer Institute ; Buffalo, NY USA.
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
authors.affiliation: Winthrop-University Hospital ; Mineola, NY USA.
authors.forename: Jeannine A
authors.initials: JA
authors.lastname: Villella
authors.affiliation: Mary Crowley Cancer Research Center ; Dallas, TX USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Nemunaitis
authors.affiliation: Duke University Medical Center ; Durham, NC USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morse
authors.affiliation: Oregon Health & Science University ; Portland, OR USA.
authors.forename: Tanja
authors.initials: T
authors.lastname: Pejovic
authors.affiliation: QEII Health Sciences Center ; Halifax, Nova Scotia, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Bentley
authors.affiliation: International Drug Development Institute (IDDI) ; Louvain la Neuve, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
authors.affiliation: Immunovaccine, Inc. ; Halifax, Nova Scotia, Canada.
authors.forename: Rita
authors.initials: R
authors.lastname: Nigam
authors.affiliation: Immunovaccine, Inc. ; Halifax, Nova Scotia, Canada.
authors.forename: Genevieve M
authors.initials: GM
authors.lastname: Weir
authors.affiliation: Immunovaccine, Inc. ; Halifax, Nova Scotia, Canada.
authors.forename: Lisa D
authors.initials: LD
authors.lastname: MacDonald
authors.affiliation: Immunovaccine, Inc. ; Halifax, Nova Scotia, Canada.
authors.forename: Tara
authors.initials: T
authors.lastname: Quinton
authors.affiliation: Immunovaccine, Inc. ; Halifax, Nova Scotia, Canada.
authors.forename: Rajkannan
authors.initials: R
authors.lastname: Rajagopalan
authors.affiliation: Immunovaccine, Inc. ; Halifax, Nova Scotia, Canada.
authors.forename: Kendall
authors.initials: K
authors.lastname: Sharp
authors.affiliation: Immunovaccine, Inc. ; Halifax, Nova Scotia, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Penwell
authors.affiliation: Immunovaccine, Inc. ; Halifax, Nova Scotia, Canada.
authors.forename: Leeladhar
authors.initials: L
authors.lastname: Sammatur
authors.affiliation: International Drug Development Institute (IDDI) ; Louvain la Neuve, Belgium.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Burzykowski
authors.affiliation: Immunovaccine, Inc. ; Halifax, Nova Scotia, Canada.
authors.forename: Marianne M
authors.initials: MM
authors.lastname: Stanford
authors.affiliation: Immunovaccine, Inc. ; Halifax, Nova Scotia, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Mansour
keywords: DepoVax; T cells; cancer; immunotherapy; survivin