Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer

James L. Gulley, Philip M. Arlen, Anne Bastian, Steven Morin, Jennifer Marte, Patricia Beetham, Kwong Yok Tsang, Junko Yokokawa, James W. Hodge, Cynthia Ménard, Kevin Camphausen, C. Norman Coleman, Francis Sullivan, Seth M. Steinberg, Jeffrey Schlom, William Dahut

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Many patients with clinically localized prostate cancer develop biochemical failure despite excellent local therapy perhaps due to occult metastatic disease. One potential solution is the utilization of a well-tolerated systemic therapy (e.g., vaccine) in concert with local therapy. Experimental Design: We present a randomized phase II clinical trial designed to determine if a poxviral vaccine encoding prostate-specific antigen (PSA) can induce a PSA-specific T-cell response when combined with radiotherapy in patients with clinically localized prostate cancer. Thirty patients were randomized in a 2:1 ratio into vaccine plus radiotherapy or radiotherapy-only arms. Those patients in the combination arm received a "priming" vaccine with recombinant vaccinia (rV) PSA plus rV containing the T-cell costimulatory molecule B7.1 (rV-B7.1) followed by monthly booster vaccines with recombinant fowlpox PSA. The vaccines were given with local granulocyte- macrophage colony-stimulating factor and low-dose systemic interleukin-2. Standard external beam radiation therapy was given between the fourth and the sixth vaccinations. Results: Seventeen of 19 patients in the combination arm completed all eight vaccinations and 13 of these 17 patients had increases in PSA-specific T cells of at least 3-fold versus no detectable increases in the radiotherapy-only arm (P < 0.0005). There was also evidence of de novo generation of T cells to well-described prostate-associated antigens not found in the vaccine, providing indirect evidence of immune-mediated tumor killing. The vaccine was well tolerated. Conclusion: This vaccine regimen can be safety given in patients undergoing radiation therapy for localized prostate cancer, with the majority of patients generating a PSA-specific cellular immune response to vaccine.

Original languageEnglish (US)
Pages (from-to)3353-3362
Number of pages10
JournalClinical Cancer Research
Volume11
Issue number9
DOIs
StatePublished - May 1 2005

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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