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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 3/2012

01-03-2012 | Original article

A gynecologic oncology group phase II trial of two p53 peptide vaccine approaches: subcutaneous injection and intravenous pulsed dendritic cells in high recurrence risk ovarian cancer patients

Authors: Osama E. Rahma, Ed Ashtar, Malgorzata Czystowska, Marta E. Szajnik, Eva Wieckowski, Sarah Bernstein, Vincent E. Herrin, Mortada A. Shams, Seth M. Steinberg, Maria Merino, William Gooding, Carmen Visus, Albert B. DeLeo, Judith K. Wolf, Jeffrey G. Bell, Jay A. Berzofsky, Theresa L. Whiteside, Samir N. Khleif

Published in: Cancer Immunology, Immunotherapy | Issue 3/2012

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Abstract

Purpose

Peptide antigens have been administered by different approaches as cancer vaccine therapy, including direct injection or pulsed onto dendritic cells; however, the optimal delivery method is still debatable. In this study, we describe the immune response elicited by two vaccine approaches using the wild-type (wt) p53 vaccine.

Experimental design

Twenty-one HLA-A2.1 patients with stage III, IV, or recurrent ovarian cancer overexpressing the p53 protein with no evidence of disease were treated in two cohorts. Arm A received SC wt p53:264-272 peptide admixed with Montanide and GM-CSF. Arm B received wt p53:264-272 peptide-pulsed dendritic cells IV. Interleukin-2 (IL-2) was administered to both cohorts in alternative cycles.

Results

Nine of 13 patients (69%) in arm A and 5 of 6 patients (83%) in arm B developed an immunologic response as determined by ELISPOT and tetramer assays. The vaccine caused no serious systemic side effects. IL-2 administration resulted in grade 3 and 4 toxicities in both arms and directly induced the expansion of T regulatory cells. The median overall survival was 40.8 and 29.6 months for arm A and B, respectively; the median progression-free survival was 4.2 and. 8.7 months, respectively.

Conclusion

We found that using either vaccination approach generates comparable specific immune responses against the p53 peptide with minimal toxicity. Accordingly, our findings suggest that the use of less demanding SC approach may be as effective. Furthermore, the use of low-dose SC IL-2 as an adjuvant might have interfered with the immune response. Therefore, it may not be needed in future trials.
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Metadata
Title
A gynecologic oncology group phase II trial of two p53 peptide vaccine approaches: subcutaneous injection and intravenous pulsed dendritic cells in high recurrence risk ovarian cancer patients
Authors
Osama E. Rahma
Ed Ashtar
Malgorzata Czystowska
Marta E. Szajnik
Eva Wieckowski
Sarah Bernstein
Vincent E. Herrin
Mortada A. Shams
Seth M. Steinberg
Maria Merino
William Gooding
Carmen Visus
Albert B. DeLeo
Judith K. Wolf
Jeffrey G. Bell
Jay A. Berzofsky
Theresa L. Whiteside
Samir N. Khleif
Publication date
01-03-2012
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 3/2012
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-011-1100-9

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