Assessment of immunological biomarkers in patients with advanced cancer treated by personalized peptide vaccination.

Abstract

e13043 Background: To investigate immunological biomarkers to predict overall survival of advanced cancer patients under treatment with personalized peptide vaccination. Methods: Between October 2000 and October 2008, pre- and post- (sixth) vaccination peripheral blood lymphocytes and plasma from 500 advanced cancer patients under treatment with personalized peptide vaccination were analyzed for measurement of cytotoxic T lymphocyte (CTL) activity and IgG reactive to the vaccinated peptides, respectively. All 500 patients suffered from advanced cancer originating in the prostate (n = 174), colon and rectum (n = 74), pancreas (n = 50), stomach (n = 42), brain (n = 33), uterus (n = 28), lung (n = 22), kidney (n = 13), skin (n = 12), breast (n = 11), bladder and urinary tracts (n = 10), and elsewhere (n = 31).Correlations between overall survival and CTL or IgG response were investigated statistically. Results: The best clinical responses were for 43 PR, 144 SD, and 249 PD with a median overall survival of 9.9 months. Increased CTL or IgG response to at least one of the vaccinated peptides was observed in 199 of 332 (60%) or 187 of 300 (62%) patients tested, respectively. IgG response (P = 0.0015) was superior to CTL response (p = 0.167) with regard to correlation with overall survival. To statistically confirm the superiority of IgG response, the samples from advanced hormone-refractory prostate cancer patients (n = 20) who survived more than 900 days and those from those (n = 23) who died within 300 days were analyzed further. As a result, the number of peptides and the increase in IgG levels were found to be significantly higher in long-term survivors (p = 0.000282 and p = 0.00045, respectively). In contrast, those of CTL responses were not statistically different between the two groups. Conclusions: The measurement of IgG response was suggested as an immunological biomarker for prediction of the overall survival of advanced cancer patients under treatment with personalized peptide vaccination. No significant financial relationships to disclose.