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Induction of specific T cell immunity in patients with prostate cancer by vaccination with PSA146–154 peptide

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Abstract

T cell immunotherapy of prostate cancer (CaP) offers the potential for less toxic, more effective outcomes. A clinical trial was conducted in 28 patients with locally advanced or metastatic CaP to determine whether an HLA-A2 binding epitope of prostate-specific antigen, PSA146–154 (PSA-peptide), can induce specific T cell immunity. Patients were vaccinated either by intradermal injection of PSA-peptide and GM-CSF or by intravenous administration of autologous dendritic cells pulsed with PSA-peptide at weeks 1, 4 and 10. Delayed-type hypersensitivity (DTH) skin testing was performed at weeks 4, 14, 26 and 52. Fifty percent of the patients developed positive DTH responses to PSA-peptide. The size of the DTH induration progressively increased over time in the majority of responding patients. Skin biopsies from seven DTH-positive patients were available and T cells that developed in situ were also characterized. The phenotype of recovered T cells demonstrated variable proportions of CD4+CD8−, CD4−CD8+ and CD4+CD8+ T cell populations. Cytokine analysis of PSA-peptide stimulated T cells per bead array assay exhibited specific IFN-γ and TNF-α response in six of seven patients. Specific IL-4 response was observed in five patients, while IL-10 response was detected in one patient. Purified CD4−CD8+ T cells isolated from four patients demonstrated specific cytolytic activity per chromium release assay. In conclusion, immunization with PSA-peptide induced specific T cell immunity in one-half of the patients with locally advanced and hormone-sensitive, metastatic CaP. DTH-derived T cells exhibited PSA-peptide-specific cytolytic activity and predominantly expressed a type-1 cytokine profile.

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Abbreviations

CaP:

Prostate cancer

CBA:

Cytokine bead array

CRA:

Chromium release assay

DC:

Dendritic cells

DMSO:

Dimethyl sulfoxide

DTH:

Delayed-type hypersensitivity

PSA:

Prostate-specific antigen

PSA:

Peptide-PSA146–154 peptide

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Acknowledgements

This work was supported by the National Cancer Institute (CA88062), the Department of Army (DAMD17-98-1-8489), the American Cancer Society (IRG 99-224-01), the Illinois Department of Public Health (prostate cancer research fund 4328301), the Cancer Research Institute, New York City, and the General Clinical Research Center of University of Illinois, Chicago, funded by NIH grant M01-RR-13987. The contents in the manuscript are solely the responsibility of the authors and do not necessarily reflect the official views of the respective funding agencies. The authors would like to thank Susan Nishimura and Susan Cascio for their excellent clinical assistance.

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Authors and Affiliations

  1. Department of Medicine, Section of Hematology/Oncology, University of Illinois, Room 3150, Molecular Biology Research Building, 900 South Ashland Avenue, Chicago, IL, 60607, USA

    Supriya Perambakam, Sigrun Hallmeyer, Samarth Reddy, Nadim Mahmud, Delores Mahmud, Rafael Nunez & David J. Peace

  2. Department of Pharmacy, University of Illinois, Chicago, IL, 60607, USA

    Linda Bressler

  3. Department of Pathology, University of Illinois, Chicago, IL, 60607, USA

    Phillip DeChristopher & Rafael Nunez

  4. Department of Medicine, Vanderbilt University, Nashville, TN, 37232, USA

    Jeffrey A. Sosman

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  1. Supriya Perambakam
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  2. Sigrun Hallmeyer
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  4. Nadim Mahmud
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  9. Jeffrey A. Sosman
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  10. David J. Peace
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Correspondence to Supriya Perambakam.

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Perambakam, S., Hallmeyer, S., Reddy, S. et al. Induction of specific T cell immunity in patients with prostate cancer by vaccination with PSA146–154 peptide. Cancer Immunol Immunother 55, 1033–1042 (2006). https://doi.org/10.1007/s00262-005-0090-x

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  • DOI: https://doi.org/10.1007/s00262-005-0090-x

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