A Phase I Trial of Pox PSA vaccines (PROSTVAC<sup>®</sup>-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOM™) in Patients with Prostate Cancer

<p>Abstract</p> <p>Purpose</p> <p>Based 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...

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Main Authors: Lattime E, Israeli R, Petrylak DP, Kaufman H, Plante M, DiPaola RS, Manson K, Schuetz T
Format: Article
Language:English
Published: BMC 2006-01-01
Series:Journal of Translational Medicine
Subjects:
PSA
Online Access:http://www.translational-medicine.com/content/4/1/1
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spelling doaj-a916471698e74b47be6ee130e3f7e7af2020-11-24T21:27:00ZengBMCJournal of Translational Medicine1479-58762006-01-0141110.1186/1479-5876-4-1A Phase I Trial of Pox PSA vaccines (PROSTVAC<sup>®</sup>-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOM™) in Patients with Prostate CancerLattime EIsraeli RPetrylak DPKaufman HPlante MDiPaola RSManson KSchuetz T<p>Abstract</p> <p>Purpose</p> <p>Based 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.</p> <p>Methods</p> <p>In this study, ten patients with androgen independent prostate cancer with or without metastatic disease were enrolled. Patients were treated with 2 × l0<sup>8 </sup>pfu of a recombinant vaccinia virus vaccine (PROSTVAC-V) followed by 1 × 10<sup>9 </sup>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).</p> <p>Results</p> <p>There 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.</p> <p>Conclusion</p> <p>This 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.</p> http://www.translational-medicine.com/content/4/1/1PSAProstate specific antigenvaccineco-stimulatory molecules
collection DOAJ
language English
format Article
sources DOAJ
author Lattime E
Israeli R
Petrylak DP
Kaufman H
Plante M
DiPaola RS
Manson K
Schuetz T
spellingShingle Lattime E
Israeli R
Petrylak DP
Kaufman H
Plante M
DiPaola RS
Manson K
Schuetz T
A Phase I Trial of Pox PSA vaccines (PROSTVAC<sup>®</sup>-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOM™) in Patients with Prostate Cancer
Journal of Translational Medicine
PSA
Prostate specific antigen
vaccine
co-stimulatory molecules
author_facet Lattime E
Israeli R
Petrylak DP
Kaufman H
Plante M
DiPaola RS
Manson K
Schuetz T
author_sort Lattime E
title A Phase I Trial of Pox PSA vaccines (PROSTVAC<sup>®</sup>-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOM™) in Patients with Prostate Cancer
title_short A Phase I Trial of Pox PSA vaccines (PROSTVAC<sup>®</sup>-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOM™) in Patients with Prostate Cancer
title_full A Phase I Trial of Pox PSA vaccines (PROSTVAC<sup>®</sup>-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOM™) in Patients with Prostate Cancer
title_fullStr A Phase I Trial of Pox PSA vaccines (PROSTVAC<sup>®</sup>-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOM™) in Patients with Prostate Cancer
title_full_unstemmed A Phase I Trial of Pox PSA vaccines (PROSTVAC<sup>®</sup>-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOM™) in Patients with Prostate Cancer
title_sort phase i trial of pox psa vaccines (prostvac<sup>®</sup>-vf) with b7-1, icam-1, and lfa-3 co-stimulatory molecules (tricom™) in patients with prostate cancer
publisher BMC
series Journal of Translational Medicine
issn 1479-5876
publishDate 2006-01-01
description <p>Abstract</p> <p>Purpose</p> <p>Based 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.</p> <p>Methods</p> <p>In this study, ten patients with androgen independent prostate cancer with or without metastatic disease were enrolled. Patients were treated with 2 × l0<sup>8 </sup>pfu of a recombinant vaccinia virus vaccine (PROSTVAC-V) followed by 1 × 10<sup>9 </sup>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).</p> <p>Results</p> <p>There 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.</p> <p>Conclusion</p> <p>This 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.</p>
topic PSA
Prostate specific antigen
vaccine
co-stimulatory molecules
url http://www.translational-medicine.com/content/4/1/1
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