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

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Abstract
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. Prostate 57: 80–92, 2003.