Induction of cytotoxic T lymphocytes from peripheral blood of human histocompatibility antigen (HLA)-A31(+) gastric cancer patients by in vitro stimulation with antigenic peptide of signet ring cell carcinoma.
Antigenic peptides have been used as a cancer vaccine in melanoma patients and have led to a drastic regression of metastatic tumors. However, few antigens have been identified in non-melanoma tumors. We recently purified a new natural antigenic peptide, designated F4. 2, by biochemical elution from a human gastric signet cell carcinoma cell line and showed that it is recognized by an autologous human histocompatibility antigen (HLA)-A31-restricted cytotoxic T lymphocyte (CTL) clone. Here we describe in vitro induction of F4. 2-specific CTLs from peripheral blood T lymphocytes of HLA-A31( +) gastric cancer patients. The T cells of seven HLA-A31( +) patients with gastric cancers were stimulated in vitro by F4.2-pulsed autologous dendritic cells which had been induced from peripheral blood of each patient by incubation in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF) and IL-4. We tested the cytotoxicity of the T cells against F4.2-loaded C1R-A*31012 by a 6-h (51)Cr release assay after 3 stimulations with F4.2-pulsed dendritic cells. F4.2-specific cytotoxicity was detectable in the stimulated T cells from two of the seven HLA-A31( +) patients. Further, both F4.2-specific CTLs also lysed the gastric cancer cell line, HST-2, from which F4.2 was derived. These results suggest that F4.2 peptide may be useful as an HLA-A31-restricted peptide vaccine in certain patients with gastric cancer.
Nabeta
Y
Y
Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan.
Sahara
H
H
Suzuki
K
K
Kondo
H
H
Nagata
M
M
Hirohashi
Y
Y
Sato
Y
Y
Wada
Y
Y
Sato
T
T
Wada
T
T
Yamashita
T
T
Kikuchi
K
K
Sato
N
N
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000187:drug effects / Q000276:immunology*; D018279:Carcinoma, Signet Ring Cell / Q000097:blood / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015234:HLA-A Antigens / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology* / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000097:blood / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C069527:HLA-A31 antigen; D010446:Peptide Fragments; C412085:peptide F4.2