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Cancer Immunology, Immunotherapy

, Volume 61, Issue 5, pp 629–641 | Cite as

Phase I/II randomized trial of dendritic cell vaccination with or without cyclophosphamide for consolidation therapy of advanced ovarian cancer in first or second remission

  • Christina S. ChuEmail author
  • Jean Boyer
  • Daniel S. Schullery
  • Phyllis A. Gimotty
  • Victoria Gamerman
  • James Bender
  • Bruce L. Levine
  • George Coukos
  • Stephen C. Rubin
  • Mark A. Morgan
  • Robert H. Vonderheide
  • Carl H. June
Original Article

Abstract

Purpose

In spite of increased rates of complete response to initial chemotherapy, most patients with advanced ovarian cancer relapse and succumb to progressive disease. Immunotherapy may have potential for consolidation therapy.

Experimental design

This randomized open-label phase I/II trial evaluated responses of patients with advanced ovarian cancer in remission for vaccination with monocyte-derived dendritic cells (DC) loaded with Her2/neu, hTERT, and PADRE peptides, with or without low-dose intravenous cyclophosphamide. All patients also received pneumococcal vaccine and were randomized to cyclophosphamide 2 days prior to first vaccination. Blood samples were analyzed by ELISPOT and flow cytometry.

Results

Of 11 patients, 2 recurred during vaccination. Nine received all 4 doses: 3 patients recurred at 6, 17, and 26 months, respectively, and 6 have no evidence of disease at 36 months. No grade 3/4 vaccine-related toxicities were noted. The 3-year overall survival was 90%. Patients receiving cyclophosphamide showed a non-significant improvement in survival over controls. Patients receiving cyclophosphamide had a transient reduction in neutrophils, but no change in total lymphocytes or regulatory T cells. Modest T-cell responses to Her2/neu and hTERT were seen post-vaccine by IFN-γ ELISPOT. Patients demonstrated below normal responses to the diphtheria conjugate protein CRM197, a component of the pneumococcal vaccine.

Conclusions

In this setting, peptide-loaded DC vaccination elicits modest immune responses, but survival is promising. Pneumococcal vaccination revealed substantial immune suppression, even in patients in remission. Rational design of consolidative strategies for ovarian cancer will need to overcome tolerance and immunosuppression.

Keywords

Ovarian cancer Dendritic cell Vaccine Clinical trial Consolidation therapy 

Notes

Acknowledgments

We are grateful for the support from Bonnie Mills at IDM, Inc. This study is dedicated to the memories of Cynthia R. June and Richard G. Carroll. In addition, we thank members of the Human Immunology Core (Abramson Cancer Center) for analysis of patient samples, and patients in the Ovarian Cancer Research Center for participating in this research protocol. This study is financially supported by NIH grants R21CA115049 (CC), 5P50CA083638 SPORE in Ovarian Cancer (GC PAG and CHJ), Cancer Biostatistics Training Grant T32CA093283 and the Ovarian Cancer Research Fund (GC and CHJ).

Conflict of interest

None.

Supplementary material

262_2011_1081_MOESM1_ESM.pptx (243 kb)
Supplementary material 1 (PPTX 242 kb)
262_2011_1081_MOESM2_ESM.pptx (267 kb)
Supplementary material 2 (PPTX 267 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Christina S. Chu
    • 1
    • 8
    Email author
  • Jean Boyer
    • 2
  • Daniel S. Schullery
    • 2
  • Phyllis A. Gimotty
    • 4
  • Victoria Gamerman
    • 4
  • James Bender
    • 3
    • 5
  • Bruce L. Levine
    • 2
  • George Coukos
    • 1
  • Stephen C. Rubin
    • 1
  • Mark A. Morgan
    • 6
  • Robert H. Vonderheide
    • 7
  • Carl H. June
    • 2
  1. 1.Department of Obstetrics and Gynecology and Ovarian Cancer Research Center, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of Pathology and Laboratory Medicine and Abramson Cancer Center, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Immuno-Designed Molecules, Inc.IrvineUSA
  4. 4.Department of Biostatistics, Center for Clinical Epidemiology and BiostatisticsUniversity of PennsylvaniaPhiladelphiaUSA
  5. 5.ImmunoCellular TherapeuticsWoodland HillsUSA
  6. 6.Department of Surgical OncologyFox Chase Cancer CenterPhiladelphiaUSA
  7. 7.Department of Medicine and Abramson Cancer Center, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  8. 8.Perelman Center for Advanced Medicine at Penn3 West Pavilion Jordan Center for Gynecologic CancerPhiladelphiaUSA

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