Immunological evaluation of personalized peptide vaccination with gemcitabine for advance pancreatic cancer patients

14029 Background: A phase I clinical study was performed to determine safety and immunogenicity of personalized peptide vaccination with gemcitabine (GEM) in advanced pancreatic cancer patients (APC). Methods: Thirteen human histocompatibility leukocyte antigen (HLA)-A24+ or A2+ patients with unresectable (n=10) or recurrent (n=3) pancreatic cancer were treated with GEM plus up to four peptides that were positive for pre-vaccination measurement of peptide-specific IgG antibodies and/or cytotoxic T lymphocyte (CTL) precursors in the circulation (personalized peptide vaccine). GEM was administered at 1000mg/m2 as a 30-min intravenous infusion once a week for three week, followed by 1 week of rest. All patients were treated on outpatient basis. The cycle was repeated every 8 weeks. Results: Peptide doses of vaccination per week were planned as follows: level 1, 1mg; level 2, 2mg; and level 3, 3mg. The main grade 3 toxicities observed during the first cycle in each level were neutropenia (15%), anemia (23%) and thrombocytopenia (15%). No significant differences in the toxicities were found between each level. There was no dose limiting toxicity (DLT) observed in each level. Augmentation of peptide-specific CTL responses in the post-vaccination peripheral blood mononuclear cells was observed in each level, while increased titer of peptide-specific IgG antibodies was observed in the post-vaccination plasma in level 2 and level 3. Applicable responses were no complete response, two partial responses (15%), and 7 stable diseases (55%). Nevertheless 7 patients of them (54%) were under the second-line chemotherapy, disease control rate was 70%, the median TTP (time to progression) was 18.5 weeks and the MST (median survival time) was 7.6 months in this study. Conclusions: The combination therapy of personalized peptide vaccination with GEM for APC patients is feasible and safe. Because of positive immune responses under a full dose of GEM, the peptide vaccination of 3 mg is recommended. No significant financial relationships to disclose.