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

Kono, Koji; Yang, Rongcun; Charo, Jehad; Ichihara, Fumiko; Celis, Esteban; Sette, Alessandro; Appella, Ettore; Sekikawa, Takayoshi; Matsumoto, Yoshirô; Kiessling, Rolf

doi:10.1002/(sici)1097-0215(19981005)78:2<202::aid-ijc14>3.3.co;2-r

Cited by 21 publications

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“…Furthermore, the HER-2 expression in HercepTest 3 þ patients was also preserved in the metastatic lymph nodes. The action of anti-HER-2-specific CTL correlated to the degree of HER-2 expression on the target tumour cells (Fisk et al, 1995;Kono et al, 1998). Also, the activity of ADCC induced by Herceptin correlated to the degree of HER-2 expression on the target tumour cells (Kono et al, 2002b).…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that HLA-A2-or HLA-A24-restricted peptide epitopes were identified for immunodominant CTL epitopes derived from HER-2 (Fisk et al, 1995;Kono et al, 1998Kono et al, , 2002b. In the present study, oesophageal SCC patients with both HLA-A24-and HER-2-positive tumours (1 þ /2 þ /3 þ ) accounted for 26% of these cases, and both HLA-A2-and HER-2-positive tumours accounted for 18% of them.…”

Section: Discussionmentioning

confidence: 99%

“…Herceptin has boosted the interest of clinicians in immunotherapy based on this molecule as it represents the first mAb approved for therapeutic use with proved survival benefit in patients with HER-2-positive breast cancer with metastasis (Baselga et al, 1996;Slamon et al, 2001). Moreover, abundant examples from experimental models and clinical trials suggest that HER-2 can be immunogenic and generate antibodies, CTL-and helper T-cell-specific responses in individuals with HER-2-overexpressing tumours (Fisk et al, 1995;Kono et al, 1998). Based on the above reports, anti-HER-2 immune targeting could be utilised as an attractive approach to treat oesophageal cancer.…”

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Frequencies of HER-2/neu expression and gene amplification in patients with oesophageal squamous cell carcinoma

et al. 2005

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The utilisation of antitumour T cells induced by cancer vaccination with HER-2 peptides or antibodies (Herceptin) against HER-2, as immunotherapy for oesophageal cancer, is a novel and attractive approach. It is important to clarify the frequencies of HER-2 expression and gene amplification in patients with oesophageal squamous cell carcinoma (SCC) and to evaluate the relationship between HER-2 status and HLA haplotype, since the candidates for HER-2 peptide-based vaccination are restricted to a certain HLA haplotype. We determined the frequency of HER-2 expression using the HercepTestt for immunohistochemistry and HER-2 gene amplification by fluorescence in situ hybridisation (FISH) assay in oesophageal SCC (n ¼ 66). HER-2-positive tumours (1 þ /2 þ /3 þ ) analysed by a HercepTest were observed in 30.3% of all the patients and HER-2 gene amplification evaluated by FISH was observed in 11.0% of all the patients, in which all HercepTest (3 þ ) tumours were found to have gene amplification and three of six moderately positive (2 þ ) tumours showed gene amplification. Furthermore, HER-2-positive cells were present more diffusely and were larger within each tumour in the patients who were HercepTest 3 þ than those who were HercepTest 1 þ . Moreover, the survival rate in HER-2-positive group was significantly worse than that in HER-2-negative group. Also, the survival rate in the patients with HER-2 gene amplification was significantly worse than that without HER-2 gene amplification. In addition, oesophageal SCC patients with both HLA-A24-positive and HER-2-positive tumours (1 þ /2 þ /3 þ ) accounted for 26% of these cases, and both HLA-A2-and HER-2-positive tumours accounted for 18% of them.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Frequencies of HER-2/neu expression and gene amplification in patients with oesophageal squamous cell carcinoma

et al. 2005

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“…27 Moreover, we reported that HER-2/neu-specific CTLs were induced from HLA-A2-positive gastric-cancer patients with HER-2/ neu-overexpressing tumors. 7 These observations suggest that T cells derived from patients with HER-2/neu-overexpressing tumors were not tolerant to HER-2/neu antigens. To what extent HER-2/neu antigens are recognized by TILs remains to be studied.…”

Section: Relationship Between Clinicopathological Features and Hla Hamentioning

confidence: 97%

“…Moreover, we have identified that HER-2/neu-derived peptides are naturally processed as tumorassociated antigens recognized by tumor-specific, HLA-A2-restricted CTLs in gastric cancer. 7 Thus, HER-2/neu-derived peptides may be considered as candidates for tumor-specific immunotherapy such as tumor vaccination in patients with gastric cancer.…”

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Frequencies of HER‐2/neu overexpression relating to HLA haplotype in patients with gastric cancer

Kono

Takahashi

Amemiya

et al. 2001

Intl Journal of Cancer

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We have identified that HER-2/neu-derived peptides are naturally processed as tumor rejection antigens recognized by tumor-specific, HLA-A2-restricted cytotoxic T lymphocytes in gastric cancer. To evaluate candidates for immunotherapy using HER-2/neu-derived, HLA-A2-restricted peptides, we examined the frequency of HLA-A2 relating to HER-2/neu overexpression or the infiltrating grade of tumorinfiltrating lymphocytes (TILs) in Japanese patients with gastric cancer. HER-2/neu-overexpressing tumors detected by immunohistochemistry amounted to 19% of primary gastric cancers and HLA-A2-positive patients with gastric cancer were 31% of primary gastric-cancer cases. Finally, gastriccancer patients with both HLA-A2-positive and HER-2/neuoverexpressing tumors amounted to 6.6% of these cases. There was no significant difference in the infiltrating grade of TILs between gastric cancers overexpressing HER-2/neu and those that did not. Gastric cancer is 1 of the most common cancers occurring in Japan today. The control of gastric cancer at advanced stages still remains difficult, despite various treatments such as gastrectomy with extensive lymphadenectomy 1 and surgery combined with chemotherapy. 2 We and others reported that MHC class I-restricted cytotoxic-T lymphocytes (CTLs) from gastric-cancer patients can react specifically against autologous tumor cells. [3][4][5][6] Adoptive immunotherapy based on gastric cancer-specific CTLs, or vaccinations based on the MHC class I-associated tumor antigens that they recognize, represent alternative therapeutic approaches. The presence of tumor-associated antigens recognized by gastric-cancer-specific CTLs restricted by HLA-A31 6 or HLA-A2.1 molecules 4 has been demonstrated, although the nature of these antigens has not been defined. Moreover, we have identified that HER-2/neu-derived peptides are naturally processed as tumorassociated antigens recognized by tumor-specific, HLA-A2-restricted CTLs in gastric cancer. 7 Thus, HER-2/neu-derived peptides may be considered as candidates for tumor-specific immunotherapy such as tumor vaccination in patients with gastric cancer.The HER-2/neu protooncogene encodes a 185-kDa transmembrane glycoprotein with tyrosine-specific kinase activity. 8 The HER-2/neu protooncogene is amplified and overexpressed in approximately 30% of human ovarian and breast tumors 9 and in 20% of gastric cancers. 10 HLA-A2-restricted CTL epitopes derived from HER2/neu recognized by ovarian-11,12 and breast-13 cancerspecific CTLs have previously been defined, in addition to those specific for gastric cancer. The identification of several new HLA-A2-restricted CTL epitopes from HER-2/neu that can activate CTLs from healthy donors and patients with advanced ovarian carcinoma has also been reported. 14,15 These results indicate that HER-2/neu-derived peptides could be broad targets for immunotherapy against these types of cancers. It is important to evaluate candidates for tumor vaccination with HER-2/neu-derived peptides in patients with gastric cancer. Because it has...

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HER-2/neu is expressed in human renal cell carcinoma at heterogeneous levels independently of tumor grading and staging and can be recognized by HLA-A2.1-restricted cytotoxic T lymphocytes

et al. 2000

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

Cited by 21 publications

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Frequencies of HER-2/neu expression and gene amplification in patients with oesophageal squamous cell carcinoma

Frequencies of HER-2/neu expression and gene amplification in patients with oesophageal squamous cell carcinoma

Frequencies of HER‐2/neu overexpression relating to HLA haplotype in patients with gastric cancer

HER-2/neu is expressed in human renal cell carcinoma at heterogeneous levels independently of tumor grading and staging and can be recognized by HLA-A2.1-restricted cytotoxic T lymphocytes

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