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

被引：82

作者：

Berinstein, Neil L. ^{[1
]}

Karkada, Mohan ^{[2
]}

Oza, Amit M. ^{[3
]}

Odunsi, Kunle ^{[4
]}

Villella, Jeannine A. ^{[5
]}

Nemunaitis, John J. ^{[6
]}

Morse, Michael A. ^{[7
]}

Pejovic, Tanja ^{[8
]}

Bentley, James ^{[9
]}

Buyse, Marc ^{[10
]}

Nigam, Rita ^{[2
]}

Weir, Genevieve M. ^{[2
]}

MacDonald, Lisa D. ^{[2
]}

Quinton, Tara ^{[2
]}

Rajagopalan, Rajkannan ^{[2
]}

Sharp, Kendall ^{[2
]}

Penwell, Andrea ^{[2
]}

Sammatur, Leeladhar ^{[2
]}

Burzykowski, Tomasz ^{[10
]}

Stanford, Marianne M. ^{[2
]}

Mansour, Marc ^{[2
]}

机构：

[1] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada

[2] Immunovaccine Inc, Halifax, NS, Canada

[3] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada

[4] Roswell Pk Canc Inst, Buffalo, NY 14263 USA

[5] Winthrop Univ Hosp, Mineola, NY 11501 USA

[6] Mary Crowley Canc Res Ctr, Dallas, TX USA

[7] Duke Univ, Med Ctr, Durham, NC USA

[8] Oregon Hlth & Sci Univ, Portland, OR 97201 USA

[9] QEII Hlth Sci Ctr, Halifax, NS, Canada

[10] IDDI, Louvain La Neuve, Belgium

来源：

ONCOIMMUNOLOGY | 2015年 / 4卷 / 08期

关键词：

cancer; DepoVax; immunotherapy; survivin; T cells; VACCINE; EFFECTOR; MEMORY; CYCLOPHOSPHAMIDE; PEPTIDE; DYSFUNCTION; RESPONSES; ADJUVANT; SITES; TRIAL;

D O I：

10.1080/2162402X.2015.1026529

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

DepoVax (TM) 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 naive 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.

引用

页数：10

共 38 条

[1] Survivin-specific T-cell reactivity correlates with tumor response and patient survival: a phase-II peptide vaccination trial in metastatic melanoma [J].

Becker, Juergen C. ;

Andersen, Mads H. ;

Hofmeister-Mueller, Valeska ;

Wobser, Marion ;

Frey, Lidia ;

Sandig, Christiane ;

Walter, Steffen ;

Singh-Jasuja, Harpreet ;

Kaempgen, Eckhart ;

Opitz, Andreas ;

Zapatka, Marc ;

Broecker, Eva-B. ;

Straten, Per Thor ;

Schrama, David ;

Ugurel, Selma .

CANCER IMMUNOLOGY IMMUNOTHERAPY, 2012, 61 (11) :2091-2103

[2] First-in-man application of a novel therapeutic cancer vaccine formulation with the capacity to induce multi-functional T cell responses in ovarian, breast and prostate cancer patients [J].

Berinstein, Neil L. ;

Karkada, Mohan ;

Morse, Michael A. ;

Nemunaitis, John J. ;

Chatta, Gurkamal ;

Kaufman, Howard ;

Odunsi, Kunle ;

Nigam, Rita ;

Sammatur, Leeladhar ;

MacDonald, Lisa D. ;

Weir, Genevieve M. ;

Stanford, Marianne M. ;

Mansour, Marc .

JOURNAL OF TRANSLATIONAL MEDICINE, 2012, 10

[3] Apoptosis-Regulated Low-Avidity Cancer-Specific CD8+ T Cells Can Be Rescued to Eliminate HER2/neu-Expressing Tumors by Costimulatory Agonists in Tolerized Mice [J].

Black, Chelsea M. ;

Armstrong, Todd D. ;

Jaffee, Elizabeth M. .

CANCER IMMUNOLOGY RESEARCH, 2014, 2 (04) :307-319

[4] Clearance of depot vaccine SPIO-labeled antigen and substrate visualized using MRI [J].

Brewer, Kimberly D. ;

Lake, Kerry ;

Pelot, Nicole ;

Stanford, Marianne M. ;

DeBay, Drew R. ;

Penwell, Andrea ;

Weir, Genevieve M. ;

Karkada, Mohan ;

Mansour, Marc ;

Bowen, Chris V. .

VACCINE, 2014, 32 (51) :6956-6962

[5] The Prioritization of Cancer Antigens: A National Cancer Institute Pilot Project for the Acceleration of Translational Research [J].

Cheever, Martin A. ;

Allison, James P. ;

Ferris, Andrea S. ;

Finn, Olivera J. ;

Hastings, Benjamin M. ;

Hecht, Toby T. ;

Mellman, Ira ;

Prindiville, Sheila A. ;

Viner, Jaye L. ;

Weiner, Louis M. ;

Matrisian, Lynn M. .

CLINICAL CANCER RESEARCH, 2009, 15 (17) :5323-5337

[6] Tumor-specific CD4+ T cells maintain effector and memory tumor-specific CD8+ T cells [J].

Church, Sarah E. ;

Jensen, Shawn M. ;

Antony, Paul A. ;

Restifo, Nicholas P. ;

Fox, Bernard A. .

EUROPEAN JOURNAL OF IMMUNOLOGY, 2014, 44 (01) :69-79

[7]

Dmitrienko A, 2010, CH CRC BIOSTAT SER, V33, P1

[8] The HIV/AIDS Vaccine Candidate MVA-B Administered as a Single Immunogen in Humans Triggers Robust, Polyfunctional, and Selective Effector Memory T Cell Responses to HIV-1 Antigens [J].

Elena Gomez, Carmen ;

Luis Najera, Jose ;

Perdiguero, Beatriz ;

Garcia-Arriaza, Juan ;

Sorzano, Carlos Oscar S. ;

Jimenez, Victoria ;

Gonzalez-Sanz, Ruben ;

Luis Jimenez, Jose ;

Angeles Munoz-Fernandez, Maria ;

Lopez Bernaldo de Quiros, Juan Carlos ;

Guardo, Alberto C. ;

Garcia, Felipe ;

Gatell, Jose M. ;

Plana, Montserrat ;

Esteban, Mariano .

JOURNAL OF VIROLOGY, 2011, 85 (21) :11468-11478

[9] Metastatic melanoma patients treated with dendritic cell vaccination, Interleukin-2 and metronomic cyclophosphamide: results from a phase II trial [J].

Ellebaek, Eva ;

Engell-Noerregaard, Lotte ;

Iversen, Trine Zeeberg ;

Froesig, Thomas Moerch ;

Munir, Shamaila ;

Hadrup, Sine Reker ;

Andersen, Mads Hald ;

Svane, Inge Marie .

CANCER IMMUNOLOGY IMMUNOTHERAPY, 2012, 61 (10) :1791-1804

[10] Immune tolerance against HBV can be overcome in HBV transgenic mice by immunization with dendritic cells pulsed by HBVsvp [J].

Farag, Mohamed M. S. ;

Tedjokusumo, Raindy ;

Flechtenmacher, Christa ;

Asen, Theresa ;

Stremmel, Wolfgang ;

Mueller, Martina ;

Protzer, Ulrike ;

Weigand, Kilian .

VACCINE, 2012, 30 (42) :6034-6039

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