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Dendritic Cells Pulsed with HER-2/neu-derived Peptides Can Induce Specific T-Cell Responses in Patients with Gastric Cancer¹

First Department of Surgery, Yamanashi Medical University, Yamanashi, 409-3898 Japan [K. K., A. T., H. S., H. F., Y. M.], and Cancer Center Karolinska Immune- and Gene Therapy Laboratory, Karolinska Hospital, S-171 76 Stockholm, Sweden [A. R. C., R. K.]

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- 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.

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