Novel breast-tumor-associated MUC1-derived peptides: Characterization in Db−/− × β2 microglobulin (β2m) null mice transgenic for a chimeric HLA-A2.1/Db-β2 microglobulin single chain

Carmon, Lior; El-Shami, Khaled; Paz, Adrian; Pascolo, Steve; Tzehoval, Esther; Tirosh, Boaz; Koren, Romelin; Feldman, Michaël; Fridkin, Mati; Lemonnier, François; Eisenbach, Lea

doi:10.1002/(sici)1097-0215(20000201)85:3<391::aid-ijc16>3.3.co;2-m

Cited by 15 publications

(26 citation statements)

References 2 publications

(2 reference statements)

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“…Viable cells (effectors) were separated by Lympholyte-M (Cedarlane, Hornby, ON, Canada) gradient, resuspended and admixed at different ratios with 5000 35 S-methioninelabelled target cells. Cytolytic assays were carried out as described previously (Carmon et al, 2000). Extracts of tumour peptides or normal colon peptides were prepared from a pool of six post-surgical colon carcinoma specimens as described before (Carmon et al, 2000).…”

Section: Vaccinationmentioning

confidence: 99%

“…We next tested 1-8D peptides for induction of anti-HCT/HHD CTL responses. HHD mice were vaccinated with the 1-8D peptides as previously described (Carmon et al, 2000). As a negative control, we used an HIV-derived peptide, TLNAWVKVV.…”

Section: The Peptides Of '1-8d Gene' Induce Anti-hct/hhd Ctl Responsesmentioning

confidence: 99%

“…These mice mount only HLA-A2.1-restricted CTL responses and were demonstrated as a useful biological tool for identifying potential TAA HLA-A2.1-restricted epitopes (Firat et al, 1999;Carmon et al, 2000;Machlenkin et al, 2005).…”

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confidence: 99%

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‘1-8 interferon inducible gene family’: putative colon carcinoma-associated antigens

et al. 2007

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D bÀ/À xb2 microglobulin (b2m) null mice transgenic for a chimeric HLA-A2.1/D b -b2m single chain (HHD mice) are an effective biological tool to evaluate the antitumour cytotoxic T-lymphocyte response of known major histocompatibility-restricted peptide tumour-associated antigens, and to screen for putative unknown novel peptides. We utilised HHD lymphocytes to identify immunodominant epitopes of colon carcinoma overexpressed genes. We screened with HHD-derived lymphocytes over 500 HLA-A2.1-restricted peptides derived from colon carcinoma overexpressed genes. This procedure culminated in the identification of seven immunogenic peptides, three of these were derived from the 'human 1-8D gene from interferon inducible gene' (1-8D). The 1-8D gene was shown to be overexpressed in fresh tumour samples. The three 1-8D peptides were both antigenic and immunogenic in the HHD mice. The peptides induce cytotoxic T lymphocytes that were able to kill a colon carcinoma cell line HCT/HHD, in vitro and retard its growth in vivo. One of the peptides shared by all the 1-8 gene family primed efficiently normal human cytotoxic T lymphocyte precursors. These results highlight the 1-8D gene and its homologues as putative immunodominant tumour-associated antigens of colon carcinoma.

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Section: Vaccinationmentioning

confidence: 99%

Section: The Peptides Of '1-8d Gene' Induce Anti-hct/hhd Ctl Responsesmentioning

confidence: 99%

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‘1-8 interferon inducible gene family’: putative colon carcinoma-associated antigens

et al. 2007

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“…In all the examined samples, the cDNA quality was assured by GAPDH expression. MAGE-A8 TAA peptides of TCC E Bar-Haim et al EL4-HHD cells were pulsed with 100 mM peptide in optiMEM at 371C for 3 h. Cytolytic assays were carried out as described previously (Carmon et al, 2000), in four effector-to-target concentrations, from 100 : 1 to 12.5 : 1. In all the experiments, the spontaneous release was o25% of maximal release.…”

Section: Vaccinationmentioning

confidence: 99%

“…HLA-A2.1 is the most widespread allele of HLA in the human population, therefore our allele of choice for the search of tumour CTL epitopes. The HHD system enabled the identification of TAA of breast carcinoma (Carmon et al, 2000(Carmon et al, , 2002, and colon carcinoma (Tirosh et al, 2003). A MAGE-A1 epitope of HLA-A2.1 was recently identified (Pascolo et al, 2001), as well as shared epitopes of MAGE genes (Graff-Dubois et al, 2002).…”

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MAGE-A8 overexpression in transitional cell carcinoma of the bladder: identification of two tumour-associated antigen peptides

et al. 2004

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Bladder carcinoma is the fourth most common cancer in men and the eighth most common cancer among women. Our study is aimed to characterise tumour-associated antigen peptides of transitional cell carcinoma of the bladder (TCC). A DNA micro-arraybased differential display analysis of 10 000 genes was carried out, and MAGE-A8 gene expression was detected in the tumour, and not in the normal bladder. High occurrence of MAGE-A8 expression was observed in fresh tumour samples (17 out of 23) and TCC lines (four of eight). The MAGE-A8 protein sequence was screened for HLA-A2.1-binding motifs, six potential peptides were synthesised, and peptides binding to HLA-A2.1 were assured. Immunogenicity and antigenicity of the MAGE-A8 peptides were examined in the HHD system, murine class I MHC knockout mice, transgenic for HLA-A2.1. The MAGE-A8 peptide immunogenicity was examined in three modes of vaccination, delivered intranasally with cholera toxin, injected into the tail base with complete Freund's adjuvant (CFA), or presented directly as loaded onto cell surface HLA-A2.1 molecules. Two peptides, 8.1 and 8.3, induce CTL that kills the T24 TCC line in vitro, and prime human lymphocyte response of healthy donors. These results demonstrate the potential use of the MAGE-A8 peptides for specific immunotherapy of TCC.

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Responses of human T cells to peptides flanking the tandem repeat and overlapping the signal sequence of MUC1

Correa

Plunkett

Coleman

et al. 2005

Intl Journal of Cancer

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The epithelial mucin MUC1 is one of the few tumour‐associated antigens identified for breast cancer. Several MUC1‐derived peptides binding HLA‐A*0201 molecules have been identified that correspond to sequences outside the tandem repeat. Immunisation with some of these peptides induces protective antitumour immunity in mice. Another HLA‐A*0201‐binding peptide has been identified in a human system. We have evaluated the CD8+ T‐cell responses to all these peptides using peripheral blood lymphocytes from breast cancer patients and normal donors. Specific CD8+ T‐cell responses could be generated in vitro against some of these peptides but only after several rounds of in vitro restimulation, and they did not recognise human cells endogenously expressing the antigen. Nevertheless, T cells recognised by HLA‐A*0201 tetramers carrying a peptide from the signal sequence (LLLLTVLTV) could be detected in the peripheral blood of some HLA‐A*0201+ breast cancer patients but not in healthy adults. This peptide is the only one of those tested which was identified in the human system, and the results emphasize the potential problems involved in translation of data from laboratory animal models to the human system. © 2005 Wiley‐Liss, Inc.

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Novel breast-tumor-associated MUC1-derived peptides: Characterization in Db−/− × β2 microglobulin (β2m) null mice transgenic for a chimeric HLA-A2.1/Db-β2 microglobulin single chain

Cited by 15 publications

References 2 publications

‘1-8 interferon inducible gene family’: putative colon carcinoma-associated antigens

‘1-8 interferon inducible gene family’: putative colon carcinoma-associated antigens

MAGE-A8 overexpression in transitional cell carcinoma of the bladder: identification of two tumour-associated antigen peptides

Responses of human T cells to peptides flanking the tandem repeat and overlapping the signal sequence of MUC1

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