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 previou...

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Bibliographic Details
Published in:Vaccine 2004-09, Vol.22 (25-26), p.3487
Main Authors: Parsons, T, Spendlove, I, Nirula, R, Writer, M, Carter, G, Carr, F, Durrant, L G
Format: Article
Language:English
Subjects:
Algorithms
Amino Acid Sequence
Amino Acid Substitution
Animals
Cancer Vaccines - genetics
Cancer Vaccines - immunology
Carcinoembryonic Antigen - genetics
Carcinoembryonic Antigen - immunology
Cell Line
Cloning, Molecular
Cytokines - biosynthesis
Cytotoxicity Tests, Immunologic
Epitopes - immunology
HLA Antigens - immunology
Humans
Immunity, Cellular - physiology
Interferon-gamma - biosynthesis
Lymphocyte Activation - drug effects
Lymphocyte Count
Mice
Molecular Mimicry
Molecular Sequence Data
Recombinant Fusion Proteins - immunology
T-Lymphocytes - immunology
T-Lymphocytes, Cytotoxic - immunology
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Summary: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.
ISSN:0264-410X