Vaccination with PSA146-154 peptide for advanced prostate cancer: A 10-year follow-up.

Abstract

e14024 Background: Prostate cancer is the second leading cause of cancer-related death among men in the United States. Although localized disease may be definitively treated with prostatectomy or radiotherapy, advanced metastatic disease can only be managed transiently with androgen-deprivation therapy (ADT) and other systemic therapies. Given the prevalence and lack of curative options for advanced disease, novel treatments warrant investigation. Methods: A study begun in 2002 at UIC examined whether vaccination against PSA146-154 peptide elicited specific T cell immunity in 28 patients with advanced disease. In order to measure immune responses, three distinct readouts were used: induction of responses to DTH skin testing for PSA146-154 peptide, detection of CD8+ PSA146-154 peptide-tetramer +T cells, and via PSA146-154 peptide-induced release of IFN-γ in pre versus post-vaccine peripheral blood mononuclear cell samples. All three assays were completed by 26 and 52 weeks following vaccination. The current study examines the long-term effects of the vaccine ten years post immunization and determines survival differences between immune responders and non-responders. Results: Individuals who demonstrated a DTH response against PSA146-154 peptide have improved survival compared to individuals who did not develop a DTH response against the peptide (80.154 months ± 7.849 v. 72.69 months ± 10.358, p = .12). By contrast, specific responses to the PSA peptide detected by IFN gamma production or tetramer staining did not correlate with improved survival. Analysis of mRNA from peripheral blood mononuclear cells of DTH responders revealed increased expression of genes involved in plasmacytoid dendritic cell function (7 genes, with .5 fold to 4.25 fold increased expression in DTH responders). Conclusions: Together, these findings suggest that vaccination against the PSA146-154 peptide may lead to improved survival in patients who effectively mount a peptide-specific DTH response. Furthermore, the RNA expression profile of responders implicates an antitumor role for plasmacytoid dendritic cells.