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

Neil L. Berinstein, Mohan Karkada, Amit M. Oza, Kunle Odunsi, Jeannine A. Villella, John J. Nemunaitis, Michael A. Morse, Tanja Pejovic, James Bentley, Marc Buyse, Rita Nigam, Genevieve M. Weir, Lisa D. MacDonald, Tara Quinton, Rajkannan Rajagopalan, Kendall Sharp, Andrea Penwell, Leeladhar Sammatur, Tomasz Burzykowski, Marianne M. Stanford & 1 others Marc Mansour

Research output: Contribution to journalArticle

39 Citations (Scopus)

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.

Original languageEnglish (US)
JournalOncoImmunology
Volume4
Issue number8
DOIs
StatePublished - Aug 3 2015

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Ovarian Neoplasms
Immunotherapy
Cell Differentiation
T-Lymphocytes
Vaccines
CD8 Antigens
Cyclophosphamide
CD4 Antigens
Cancer Vaccines
Histocompatibility Antigens Class II
Autoantigens
Neoplasm Antigens
Neoplasms
Animal Models
Drive
Safety
Peptides
Therapeutics

Keywords

  • cancer
  • DepoVax
  • immunotherapy
  • survivin
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Oncology
  • Immunology

Cite this

Survivin-targeted immunotherapy drives robust polyfunctional T cell generation and differentiation in advanced ovarian cancer patients. / Berinstein, Neil L.; Karkada, Mohan; Oza, Amit M.; Odunsi, Kunle; Villella, Jeannine A.; Nemunaitis, John J.; Morse, Michael A.; Pejovic, Tanja; Bentley, James; Buyse, Marc; Nigam, Rita; Weir, Genevieve M.; MacDonald, Lisa D.; Quinton, Tara; Rajagopalan, Rajkannan; Sharp, Kendall; Penwell, Andrea; Sammatur, Leeladhar; Burzykowski, Tomasz; Stanford, Marianne M.; Mansour, Marc.

In: OncoImmunology, Vol. 4, No. 8, 03.08.2015.

Research output: Contribution to journalArticle

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 2015, 'Survivin-targeted immunotherapy drives robust polyfunctional T cell generation and differentiation in advanced ovarian cancer patients', OncoImmunology, vol. 4, no. 8. https://doi.org/10.1080/2162402X.2015.1026529
Berinstein, Neil L. ; Karkada, Mohan ; Oza, Amit M. ; Odunsi, Kunle ; Villella, Jeannine A. ; Nemunaitis, John J. ; Morse, Michael A. ; Pejovic, Tanja ; Bentley, James ; Buyse, Marc ; Nigam, Rita ; Weir, Genevieve M. ; MacDonald, Lisa D. ; Quinton, Tara ; Rajagopalan, Rajkannan ; Sharp, Kendall ; Penwell, Andrea ; Sammatur, Leeladhar ; Burzykowski, Tomasz ; Stanford, Marianne M. ; Mansour, Marc. / Survivin-targeted immunotherapy drives robust polyfunctional T cell generation and differentiation in advanced ovarian cancer patients. In: OncoImmunology. 2015 ; Vol. 4, No. 8.
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