A novel CEA vaccine stimulates T cell proliferation, gammaIFN secretion and CEA specific CTL responses

• 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
• ISSN: 0264-410X

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.