Dendritic cells pulsed with HER-2/neu-derived peptides can induce specific T-cell responses in patients with gastric cancer.
OBJECTIVE
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.


METHODS
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.
Kono
Koji
K
First Department of Surgery, Yamanashi Medical University, Yamanashi, 409-3898 Japan. kojikono@res.yamanashi-med.ac.jp
Takahashi
Akihiro
A
Sugai
Hidemitsu
H
Fujii
Hideki
H
Choudhury
A Raja
AR
Kiessling
Rolf
R
Matsumoto
Yoshiro
Y
D000328:Adult; D000368:Aged; D018395:CA-19-9 Antigen / Q000097:blood; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen / Q000097:blood; D003713:Dendritic Cells / Q000378:metabolism*; D000939:Epitopes; D015789:HLA-A2 Antigen / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000628:therapy*; D013601:T-Lymphocytes / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
D018395:CA-19-9 Antigen; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D000939:Epitopes; D015789:HLA-A2 Antigen; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases