A novel CEA vaccine stimulates T cell proliferation, gammaIFN secretion and CEA specific CTL responses.
Carcinoembryonic antigen (CEA) is a cell surface protein over-expressed by a wide range of tumours. The mouse anti-idiotypic antibody, 708, mimics CEA and can induce both antibody and T cell responses that specifically recognise this antigen. Sequence analysis of 708 revealed homology with a previously identified HLA-A3 T cell epitope in CEA but not to other closely related molecules. 708 was chimerised to a human IgG1 to allow Fc targeting of APCs and was deimmunised to remove unwanted T cell epitopes. The chimerised and deimmunised, but not the mouse 708, could stimulate CTL, proliferation and gammaIFN responses in vitro in normal (HLA-A3, DR1) individuals. Furthermore, the CTLs killed tumour cells expressing CEA suggesting that this deimmunised antibody could be a useful vaccine for solid tumours.
CRC Academic Department of Clinical Oncology, University of Nottingham, City Hospital, Hucknall Road, Nottingham NG5 1PB, UK.
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Parsons
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Spendlove
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Nirula
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Writer
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Carter
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Carr
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Durrant
D000465:Algorithms; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D003001:Cloning, Molecular; D016207:Cytokines / Q000096:biosynthesis; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D051379:Mice; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D016207:Cytokines; D000939:Epitopes; D006680:HLA Antigens; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma