Abstract P4-06-06: Comparison of the immunological and clinical effect of personalized peptide vaccination for patients with breast cancer

Abstract

Abstract Background: Selected therapeutic personalized peptide vaccines (PPV) were effective for boosting anticancer immune response that was associated with the clinical outcome as a prognostic factor for metastatic recurrent breast cancer (mrBC) 1-2. In this study, we investigated the immunological and clinical effect of PPV as the prophylactic cancer vaccine for non-recurrent but high-risk BC (nrhrBC) patients (pts), and we compared it's features to those of the mrBC pts who had active cancers or became resistant to the standard therapies(TR-mrBC). Methods: Material and Patient eligibility criteria: The peptides were selected from the 31 PPVs according to the results of HLA typing and peptide-specific IgG titers. Pts with a histological diagnosis of BC and their HLA-A molecules should be each of -A2, A3, A11, A24, A26, A31 or A33. The clinical protocols were approved by the institutional review board. (UMIN000003081and 00000184400000). Treatment schedule: A maximum of 4 peptides was administrated as weekly for initial four vaccinations and as biweekly for further inoculations. The concomitant standard endocrine therapy and the chemo-endocrine therapy were available for nrhrBC pts after finishing the standard adjuvant chemotherapy, and for mrBC pts concurrently. Immune and clinical response assessment: Specific T-cell responses, IgG titers and cytokines were evaluated using by interferon (IFN)-γ ELISPOT, Luminex assay and ELISA system in every 6-8 vaccinations. Toxicity, clinical response and correlation with the immune responses were investigated. Results: 16 pts with nrhrBC, 41 pts with mrBC and 79 pts with TR-mrBC received median 18, 16 and 14 vaccines, respectively. After PPV therapies, peptide-specific IgG and CTLs increased significantly in a total of 47 (77%) and 37(60%) in nrhrBC pts, 102 (63%) and 98 (61%) in mrBC pts, and 150(53%) and 100 (42%) in TR-mrBC pts. Pts experienced Grade 1-3 skin reaction at injection site, no other grade 3 or 4 SAEs were associated with PPV but with the disease progression or combination therapy. The median time to progression (TTP) and overall survival (OS) were not reached in nrhrBC pts, 7.8 and 29 months in mrBC pts, and were 7.5 and 15.9 months in TR-mrBC pts, respectively. The peptide specific CTL response was correlated significantly with OS in nrhrBC pts and the IgG levels were associated with the better OS in either non TR-mrBC pts or TR-mrBC pts. High levels of IL-6, GM-CSF, IFN-g, IL-2 receptor, BAFF were associated with worse prognosis for pts with TR-mrBC. And high levels of GM-CSF and BAFF were associated with worse prognosis for pts with nrhrBC and mrBC, respectively. In contrast, High levels of IL-2 were associated with the better prognosis for pts with mrBC. Conclusion: This study indicated that immunological features of these three groups were different from each other with most potent PPV-induced immune boosting for nrhrBC pts. Pts with mrBC who had lower immune-suppressive cytokine levels had the better prognosis. These results suggested the PPV therapy could be effective for postoperative prophylactic vaccination in patients with nrhrBC.