Induction of cellular and humoral immune responses to tumor cells and peptides in HLA-A24 positive hormone-refractory prostate cancer patients by peptide vaccination

BACKGROUND. To assess the safety and immune response of a peptide-based immunotherapy for patients with hormone-refractory prostate cancer, a phase I clinical trial was conducted. METHODS. This study first investigated whether cytotoxic T-lymphocyte (CTL) precursors reacting to peptide with vaccine candidates (14 peptides for HLA-A24 positive patients) were detectable in the pre-vaccination peripheral blood mononuclear cells (PBMCs) of ten patients with hormone-refractory prostate cancer. Patients were then vaccinated subcutaneously with only those peptides to which pre-vaccination PBMCs reacted (CTL precursor-oriented peptide vaccine) for up to four kinds of peptides. RESULTS. Overall vaccinations were generally well tolerated, but most patients (nine of ten) developed grade 1 local redness and swelling at the injection site. Increased CTL response to both peptides and cancer cells were observed in four of ten patients. Anti-peptide IgG antibodies were also detected in post-vaccination sera of seven of ten patients. One patient achieved a partial response with an 89% decrease in PSA. Stable disease was demonstrated in five of ten patients (50%) for the median duration of 2 months (range, 2-5 months). There were no objective responses of measurable lesions. CONCLUSIONS. Increase in cellular and humoral immune responses, and decrease in PSA level in some patients support further development of peptide-based immunotherapy for hormone refractory prostate cancer. (C) 2003 Wiley-Liss, Inc.