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Phase I study of intraprostatic vaccine administration in men with locally recurrent or progressive prostate cancer

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Abstract

The primary end point of this study was to determine the safety and feasibility of intraprostatic administration of PSA-TRICOM vaccine [encoding transgenes for prostate-specific antigen (PSA) and 3 costimulatory molecules] in patients with locally recurrent or progressive prostate cancer. This trial was a standard 3 + 3 dose escalation with 6 patients each in cohorts 4 and 5 to gather more immunologic data. Nineteen of 21 patients enrolled had locally recurrent prostate cancer after definitive radiation therapy, and 2 had no local therapy. All cohorts received initial subcutaneous vaccination with recombinant vaccinia (rV)-PSA-TRICOM and intraprostatic booster vaccinations with recombinant fowlpox (rF)-PSA-TRICOM. Cohorts 3–5 also received intraprostatic rF-GM-CSF. Cohort 5 received additional subcutaneous boosters with rF-PSA-TRICOM and rF-GM-CSF. Patients had pre- and post-treatment prostate biopsies, and analyses of peripheral and intraprostatic immune cells were performed. There were no dose-limiting toxicities, and the maximum tolerated dose was not reached. The most common grade 2 adverse events were fever (38 %) and subcutaneous injection site reactions (33 %); the single grade 3 toxicity was transient fever. Overall, 19 of 21 patients on trial had stable (10) or improved (9) PSA values. There was a marked increase in CD4+ (p = 0.0002) and CD8+ (p = 0.0002) tumor infiltrates in post- versus pre-treatment tumor biopsies. Four of 9 patients evaluated had peripheral immune responses to PSA or NGEP. Intraprostatic administration of PSA-TRICOM is safe and feasible and can generate a significant immunologic response. Improved serum PSA kinetics and intense post-vaccination inflammatory infiltrates were seen in the majority of patients. Clinical trials examining clinical end points are warranted.

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Acknowledgments

Grant support was provided by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. The authors thank Benedetto Farsaci and Caroline Jochems for their helpful discussions, Diane J. Poole for her technical assistance, and Bonnie L. Casey and Debra Weingarten for their editorial assistance in the preparation of this manuscript.

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The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Dr., 8B09 MSC 1750, Bethesda, MD, 20892, USA

    James L. Gulley, Christopher R. Heery, Ravi A. Madan, Kwong-Yok Tsang & Jeffrey Schlom

  2. Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Beatriz A. Walter & Maria J. Merino

  3. Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    William L. Dahut

  4. Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Peter A. Pinto

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  1. James L. Gulley
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Gulley, J.L., Heery, C.R., Madan, R.A. et al. Phase I study of intraprostatic vaccine administration in men with locally recurrent or progressive prostate cancer. Cancer Immunol Immunother 62, 1521–1531 (2013). https://doi.org/10.1007/s00262-013-1448-0

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