Long-Term Follow-Up of HLA-A2+ Patients with High-Risk, Hormone-Sensitive Prostate Cancer Vaccinated with the Prostate Specific Antigen Peptide Homologue (PSA146-154)

Supriya Perambakam,David J Peace,Seby Edassery,Hui Xie

doi:10.1155/2010/473453

Abstract

Twenty-eight HLA-A2+ patients with high-risk, locally advanced or metastatic, hormone-sensitive prostate cancer were immunized with a peptide homologue of prostate-specific antigen, PSA146-154, between July 2002 and September 2004 and monitored for clinical and immune responses. Fifty percent of the patients developed strong PSA146-154-peptide-specific delayed-type hypersensitivity skin responses, tetramer and/or IFN-γ responses within one year. Thirteen patients had stable or declining serum levels of PSA one year post-vaccination. A decreased risk of biochemical progression was observed in patients who developed augmented tetramer responses at six months compared to pre-vaccination levels (P = .02). Thirteen patients have died while 15 patients remain alive with a mean overall survival of 60 months (95% CI, 51 to 68 months) per Kaplan-Meier analysis. A trend towards greater overall survival was detected in men with high-risk, hormone-sensitive CaP who developed specific T-cell immunity following vaccination with PSA146-154 peptide.

Highlights

Prostate cancer (CaP) is the second leading cause of cancerrelated mortality in the United States
Recent studies have demonstrated that overall survival (OS) of patients with hormone refractory CaP can be modestly extended by vaccination with autologous dendritic cells (DC) loaded with recombinant proteins consisting of granulocyte macrophage colony stimulating factor and prostatic acid phosphatase [3]
Patients either had advanced local disease with high risk of recurrence based on the presence of T3, T4 disease, a serum Prostate-specific antigen (PSA) level ≥10 ng/ml, or a Gleason grade ≥7 (Group A), or they had confirmed metastatic disease which was associated with declining serum PSA on androgen deprivation therapy (ADT) or a stable or improving bone scan or CT scan in response to hormone therapy (Group B)

Summary

Introduction

Prostate cancer (CaP) is the second leading cause of cancerrelated mortality in the United States. Recent studies have demonstrated that overall survival (OS) of patients with hormone refractory CaP can be modestly extended by vaccination with autologous dendritic cells (DC) loaded with recombinant proteins consisting of granulocyte macrophage colony stimulating factor and prostatic acid phosphatase [3]. Prostate-specific antigen (PSA) contains an HLAA2-restricted epitope, PSA146-154, amino acid sequence KLQCVDLHV, that is an attractive candidate for specific immunotherapy of HLA-A2+ patients with CaP [4, 5]. The safety and immunogenicity of PSA146-154 peptide vaccination in patients with metastatic, hormone-sensitive CaP, or a disease that is at high risk of recurrence on the basis of tumor stage, serum PSA levels, and Gleason score have been previously reported [6]. We report the clinical outcome of patients up to eight years following vaccination and correlate patients’ survival with their immunological responses to the PSA146-154 vaccine

Methods

Results

Conclusion