Identification of HER2/neu-derived peptide epitopes recognized by gastric cancer-specific cytotoxic T lymphocytes

Koji Kono, Yang Rongcun, Jehad Charo, Fumiko Ichihara, Esteban Celis, Alessandro Sette, Ettore Appella, Takayoshi Sekikawa, Yoshiro Matsumoto, Rolf Kiessung

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

We have derived HLA-A2.1-restricted, gastric cancer-specific cytotoxic T lymphocyte (CTL) lines by repetitive in vitro stimulation of tumor- associated lymphocytes (TAL) with autologous tumor cells. The HER2/neu specificity of these gastric cancer-specific CTLs was demonstrated using HER2/neu-transfected cell lines and HER2/neu-expressing tumors, and with a set of HER2/neu-derived peptide epitopes. Gastric cancer-specific CTLs specifically lysed autologous and allogeneic HLA-A2.1 +, HER2/neu+ gastric cancer cells, HER2/neu-transfected CIR/A2 cell lines (HLA-A2.1+, HER2+) and HLA-A2.1-transfected SW626 tumor cell lines (HLA-A2.1+, HER2+). This recognition could be inhibited by anti-HLA-A2 antibody or by cold target HER2/neu-transfected CIR/A2 cells. Our results demonstrate that the HER2/neu- encoded HLA-A2.1-associated epitopes recognized by CTLs are presented as naturally processed peptides on gastric cancer lines. Furthermore, 3 of 19 tested HER2/neu-derived peptide epitopes [HER2(9106), HER2(9369), HER2(9689)], which all bound HLA-A2.1 with high (IC50 < 50 nM) affinity, were able to sensitize HLA-A2+ CIR/A2 cells to be recognized by the gastric cancer-specific CTLs, demonstrating the immunodominance of these epitopes. In conclusion, our findings implicate HER2/neu-derived epitopes as potential candidates for novel immunotherapy and vaccine strategies against gastric cancer.

Original languageEnglish (US)
Pages (from-to)202-208
Number of pages7
JournalInternational Journal of Cancer
Volume78
Issue number2
DOIs
StatePublished - Oct 8 1998

Fingerprint

Cytotoxic T-Lymphocytes
Stomach Neoplasms
Epitopes
Peptides
varespladib methyl
HLA-A2 Antigen
Cell Line
Neoplasms
Tumor Cell Line
Immunotherapy
Inhibitory Concentration 50
Vaccines
Lymphocytes
Antibodies

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Identification of HER2/neu-derived peptide epitopes recognized by gastric cancer-specific cytotoxic T lymphocytes. / Kono, Koji; Rongcun, Yang; Charo, Jehad; Ichihara, Fumiko; Celis, Esteban; Sette, Alessandro; Appella, Ettore; Sekikawa, Takayoshi; Matsumoto, Yoshiro; Kiessung, Rolf.

In: International Journal of Cancer, Vol. 78, No. 2, 08.10.1998, p. 202-208.

Research output: Contribution to journalArticle

Kono, Koji ; Rongcun, Yang ; Charo, Jehad ; Ichihara, Fumiko ; Celis, Esteban ; Sette, Alessandro ; Appella, Ettore ; Sekikawa, Takayoshi ; Matsumoto, Yoshiro ; Kiessung, Rolf. / Identification of HER2/neu-derived peptide epitopes recognized by gastric cancer-specific cytotoxic T lymphocytes. In: International Journal of Cancer. 1998 ; Vol. 78, No. 2. pp. 202-208.
@article{384b46b5a70842a88dc8a4bb08cf5a5a,
title = "Identification of HER2/neu-derived peptide epitopes recognized by gastric cancer-specific cytotoxic T lymphocytes",
abstract = "We have derived HLA-A2.1-restricted, gastric cancer-specific cytotoxic T lymphocyte (CTL) lines by repetitive in vitro stimulation of tumor- associated lymphocytes (TAL) with autologous tumor cells. The HER2/neu specificity of these gastric cancer-specific CTLs was demonstrated using HER2/neu-transfected cell lines and HER2/neu-expressing tumors, and with a set of HER2/neu-derived peptide epitopes. Gastric cancer-specific CTLs specifically lysed autologous and allogeneic HLA-A2.1 +, HER2/neu+ gastric cancer cells, HER2/neu-transfected CIR/A2 cell lines (HLA-A2.1+, HER2+) and HLA-A2.1-transfected SW626 tumor cell lines (HLA-A2.1+, HER2+). This recognition could be inhibited by anti-HLA-A2 antibody or by cold target HER2/neu-transfected CIR/A2 cells. Our results demonstrate that the HER2/neu- encoded HLA-A2.1-associated epitopes recognized by CTLs are presented as naturally processed peptides on gastric cancer lines. Furthermore, 3 of 19 tested HER2/neu-derived peptide epitopes [HER2(9106), HER2(9369), HER2(9689)], which all bound HLA-A2.1 with high (IC50 < 50 nM) affinity, were able to sensitize HLA-A2+ CIR/A2 cells to be recognized by the gastric cancer-specific CTLs, demonstrating the immunodominance of these epitopes. In conclusion, our findings implicate HER2/neu-derived epitopes as potential candidates for novel immunotherapy and vaccine strategies against gastric cancer.",
author = "Koji Kono and Yang Rongcun and Jehad Charo and Fumiko Ichihara and Esteban Celis and Alessandro Sette and Ettore Appella and Takayoshi Sekikawa and Yoshiro Matsumoto and Rolf Kiessung",
year = "1998",
month = "10",
day = "8",
doi = "10.1002/(SICI)1097-0215(19981005)78:2<202::AID-IJC14>3.0.CO;2-C",
language = "English (US)",
volume = "78",
pages = "202--208",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Identification of HER2/neu-derived peptide epitopes recognized by gastric cancer-specific cytotoxic T lymphocytes

AU - Kono, Koji

AU - Rongcun, Yang

AU - Charo, Jehad

AU - Ichihara, Fumiko

AU - Celis, Esteban

AU - Sette, Alessandro

AU - Appella, Ettore

AU - Sekikawa, Takayoshi

AU - Matsumoto, Yoshiro

AU - Kiessung, Rolf

PY - 1998/10/8

Y1 - 1998/10/8

N2 - We have derived HLA-A2.1-restricted, gastric cancer-specific cytotoxic T lymphocyte (CTL) lines by repetitive in vitro stimulation of tumor- associated lymphocytes (TAL) with autologous tumor cells. The HER2/neu specificity of these gastric cancer-specific CTLs was demonstrated using HER2/neu-transfected cell lines and HER2/neu-expressing tumors, and with a set of HER2/neu-derived peptide epitopes. Gastric cancer-specific CTLs specifically lysed autologous and allogeneic HLA-A2.1 +, HER2/neu+ gastric cancer cells, HER2/neu-transfected CIR/A2 cell lines (HLA-A2.1+, HER2+) and HLA-A2.1-transfected SW626 tumor cell lines (HLA-A2.1+, HER2+). This recognition could be inhibited by anti-HLA-A2 antibody or by cold target HER2/neu-transfected CIR/A2 cells. Our results demonstrate that the HER2/neu- encoded HLA-A2.1-associated epitopes recognized by CTLs are presented as naturally processed peptides on gastric cancer lines. Furthermore, 3 of 19 tested HER2/neu-derived peptide epitopes [HER2(9106), HER2(9369), HER2(9689)], which all bound HLA-A2.1 with high (IC50 < 50 nM) affinity, were able to sensitize HLA-A2+ CIR/A2 cells to be recognized by the gastric cancer-specific CTLs, demonstrating the immunodominance of these epitopes. In conclusion, our findings implicate HER2/neu-derived epitopes as potential candidates for novel immunotherapy and vaccine strategies against gastric cancer.

AB - We have derived HLA-A2.1-restricted, gastric cancer-specific cytotoxic T lymphocyte (CTL) lines by repetitive in vitro stimulation of tumor- associated lymphocytes (TAL) with autologous tumor cells. The HER2/neu specificity of these gastric cancer-specific CTLs was demonstrated using HER2/neu-transfected cell lines and HER2/neu-expressing tumors, and with a set of HER2/neu-derived peptide epitopes. Gastric cancer-specific CTLs specifically lysed autologous and allogeneic HLA-A2.1 +, HER2/neu+ gastric cancer cells, HER2/neu-transfected CIR/A2 cell lines (HLA-A2.1+, HER2+) and HLA-A2.1-transfected SW626 tumor cell lines (HLA-A2.1+, HER2+). This recognition could be inhibited by anti-HLA-A2 antibody or by cold target HER2/neu-transfected CIR/A2 cells. Our results demonstrate that the HER2/neu- encoded HLA-A2.1-associated epitopes recognized by CTLs are presented as naturally processed peptides on gastric cancer lines. Furthermore, 3 of 19 tested HER2/neu-derived peptide epitopes [HER2(9106), HER2(9369), HER2(9689)], which all bound HLA-A2.1 with high (IC50 < 50 nM) affinity, were able to sensitize HLA-A2+ CIR/A2 cells to be recognized by the gastric cancer-specific CTLs, demonstrating the immunodominance of these epitopes. In conclusion, our findings implicate HER2/neu-derived epitopes as potential candidates for novel immunotherapy and vaccine strategies against gastric cancer.

UR - http://www.scopus.com/inward/record.url?scp=0031712512&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031712512&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-0215(19981005)78:2<202::AID-IJC14>3.0.CO;2-C

DO - 10.1002/(SICI)1097-0215(19981005)78:2<202::AID-IJC14>3.0.CO;2-C

M3 - Article

C2 - 9754653

AN - SCOPUS:0031712512

VL - 78

SP - 202

EP - 208

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 2

ER -