Cancer Immunology, Immunotherapy

, Volume 62, Issue 9, pp 1521–1531

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

Authors

    • Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer InstituteNational Institutes of Health
  • Christopher R. Heery
    • Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer InstituteNational Institutes of Health
  • Ravi A. Madan
    • Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer InstituteNational Institutes of Health
  • Beatriz A. Walter
    • Laboratory of Pathology, Center for Cancer Research, National Cancer InstituteNational Institutes of Health
  • Maria J. Merino
    • Laboratory of Pathology, Center for Cancer Research, National Cancer InstituteNational Institutes of Health
  • William L. Dahut
    • Medical Oncology Branch, Center for Cancer Research, National Cancer InstituteNational Institutes of Health
  • Kwong-Yok Tsang
    • Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer InstituteNational Institutes of Health
  • Jeffrey Schlom
    • Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer InstituteNational Institutes of Health
  • Peter A. Pinto
    • Urologic Oncology Branch, Center for Cancer Research, National Cancer InstituteNational Institutes of Health
Original Article

DOI: 10.1007/s00262-013-1448-0

Cite this article as:
Gulley, J.L., Heery, C.R., Madan, R.A. et al. Cancer Immunol Immunother (2013) 62: 1521. doi:10.1007/s00262-013-1448-0

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.

Keywords

Cancer vaccineImmunotherapyPROSTVACIntratumoral vaccineProstate cancer

Copyright information

© Springer-Verlag Berlin Heidelberg (outside the USA) 2013