A Phase I Trial of Pox PSA vaccines PROSTVAC®-VF with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules TRICOM™ in Patients with Prostate CancerReport as inadecuate




A Phase I Trial of Pox PSA vaccines PROSTVAC®-VF with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules TRICOM™ in Patients with Prostate Cancer - Download this document for free, or read online. Document in PDF available to download.

Journal of Translational Medicine

, 4:1

First Online: 03 January 2006Received: 24 August 2005Accepted: 03 January 2006DOI: 10.1186-1479-5876-4-1

Cite this article as: DiPaola, R., Plante, M., Kaufman, H. et al. J Transl Med 2006 4: 1. doi:10.1186-1479-5876-4-1

Abstract

PurposeBased on previous studies that demonstrated the safety profile and preliminary clinical activity of prostate specific antigen PSA targeted therapeutic vaccines, as well as recent laboratory data supporting the value of the addition of co-stimulatory molecules B7-1, ICAM-1, and LFA-3 designated TRICOM™ to these vaccines, we conducted a Phase I study to evaluate the safety and immunogenicity of a novel vaccinia and fowlpox vaccine incorporating the PSA gene sequence and TRICOM.

MethodsIn this study, ten patients with androgen independent prostate cancer with or without metastatic disease were enrolled. Patients were treated with 2 × l0 pfu of a recombinant vaccinia virus vaccine PROSTVAC-V followed by 1 × 10 pfu of the booster recombinant fowlpox virus PROSTVAC-F both with gene sequences for PSA and TRICOM. The mean age of patients enrolled in the study was 70 range 63 to 79. The mean PSA at baseline was 434 range 9 – 1424.

ResultsThere were no deaths, and no Grade 3 or 4 adverse events. The most commonly reported adverse events, regardless of causality, were injection site reactions and fatigue. One serious adverse event SAE occurred that was unrelated to vaccine; this patient developed progressive disease with a new sphenoid metastasis. PSA was measured at week 4 and week 8. Four patients had stable disease with less than 25% increase in PSA through the week 8 study period. Anti-PSA antibodies were not induced with therapy: however, anti-vaccinia titers increased in all patients.

ConclusionThis study demonstrated that vaccination with PROSTVAC-V and PROSTVAC-F combined with TRICOM is well-tolerated and generated an immune response to vaccinia. Therefore, PROSTVAC-VF-TRICOM represents a feasible therapeutic approach for further phase II and III study in patients with prostate cancer.

KeywordsPSA Prostate specific antigen vaccine co-stimulatory molecules Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-4-1 contains supplementary material, which is available to authorized users.

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Author: RS DiPaola - M Plante - H Kaufman - DP Petrylak - R Israeli - E Lattime - K Manson - T Schuetz

Source: https://link.springer.com/







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