PMID- 12429626 OWN - NLM STAT- MEDLINE DCOM- 20030616 LR - 20201212 IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 8 IP - 11 DP - 2002 Nov TI - Dendritic cells pulsed with HER-2/neu-derived peptides can induce specific T-cell responses in patients with gastric cancer. PG - 3394-400 AB - PURPOSE: We have previously reported (K. Kono et al., Int. J. Cancer, 78: 202-208, 1998) that HER-2/neu-derived peptides are naturally processed as tumor-associated antigens recognized by tumor-specific, human leukocyte antigen (HLA)-A2-restricted CTLs in gastric cancer. In the present study, we described a Phase-1 vaccination trial in gastric cancer patients using dendritic cells (DCs) pulsed with the immunodominant HER-2/neu(p369) peptides. EXPERIMENTAL DESIGN: Nine enrolled patients, who had HER-2/neu-overexpressing tumors and who were HLA-A2 positive, received four vaccinations by DCs pulsed with HER-2(p369) peptide at 2-week intervals intradermally. RESULTS: There were no serious adverse effects noted in the immunized patients. Peripheral blood mononuclear cells, preimmunization and after the fourth immunization, were cultured with autologous, HER-2(p369)-pulsed antigen-presenting cells for 12 days. Thereafter, peptide specificity was evaluated by IFN-gamma secretion assay from cultured T cells against T2 cells pulsed with HER-2(p369) peptide. HER-2/neu peptide-specific recognition could be demonstrated in six of nine patients after immunization, whereas there was no HER-2/neu peptide-specific recognition before immunization. The peptide-specific CTL lines isolated from two of the patients could also lyse a HER2/neu-transfected cell line. Furthermore, a peptide-specific delayed-type hypersensitivity response occurred in three of nine patients. One of the patients underwent a partial clinical response concurrent with a decrease of tumor marker. Another patient demonstrated a stabilization of disease status for a period of 3 months. CONCLUSIONS: Taken together, tumor vaccination therapy with DCs pulsed with HER-2/neu-peptides may be a potential candidate for the novel treatment of gastric cancer patients. FAU - Kono, Koji AU - Kono K AD - First Department of Surgery, Yamanashi Medical University, Yamanashi, 409-3898 Japan. kojikono@res.yamanashi-med.ac.jp FAU - Takahashi, Akihiro AU - Takahashi A FAU - Sugai, Hidemitsu AU - Sugai H FAU - Fujii, Hideki AU - Fujii H FAU - Choudhury, A Raja AU - Choudhury AR FAU - Kiessling, Rolf AU - Kiessling R FAU - Matsumoto, Yoshiro AU - Matsumoto Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (CA-19-9 Antigen) RN - 0 (Cancer Vaccines) RN - 0 (Carcinoembryonic Antigen) RN - 0 (Epitopes) RN - 0 (HLA-A2 Antigen) RN - 0 (Peptides) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adult MH - Aged MH - CA-19-9 Antigen/blood MH - Cancer Vaccines MH - Carcinoembryonic Antigen/blood MH - Dendritic Cells/*metabolism MH - Epitopes MH - HLA-A2 Antigen/biosynthesis MH - Humans MH - Immunohistochemistry MH - Leukocytes, Mononuclear/metabolism MH - Male MH - Middle Aged MH - Peptides/chemistry/*therapeutic use MH - Receptor, ErbB-2/*therapeutic use MH - Stomach Neoplasms/*therapy MH - T-Lymphocytes/*metabolism MH - Time Factors MH - Transfection EDAT- 2002/11/14 04:00 MHDA- 2003/06/17 05:00 CRDT- 2002/11/14 04:00 PHST- 2002/11/14 04:00 [pubmed] PHST- 2003/06/17 05:00 [medline] PHST- 2002/11/14 04:00 [entrez] PST - ppublish SO - Clin Cancer Res. 2002 Nov;8(11):3394-400.