A therapeutic human anti-idiotypic antibody mimics CD55 in three distinct regions.

Abstract	The human anti-idiotypic antibody 105AD7 was isolated from a colorectal cancer patient receiving the anti-tumor antibody 791T/36 for radioimmuno-scintigraphy of liver metastases. We have mapped the binding site of 791T/36 to the first two small consensus repeat (SCR) domains of the complement regulatory protein (CD55) that is overexpressed by a wide range of solid tumors. Cloning of both antigen and anti-idiotype has identified the molecular basis of their mimicry. Amino acid homology has been identified between three complementarity-determining regions of 105AD7 and three regions of CD55 within the first two SCR domains. 791T/36 and anti-anti-idiotypic (Ab3) polyclonal antibodies raised against 105AD7 showed specific binding to these peptides. The antibodies were also found to bind synergistically to combinations of these peptides, indicating cooperativity between the peptides in stabilizing antibody binding. This also implies that the contact face on both CD55 antigen and 105AD7 is generated by the cooperation of several peptides positioned on two domains in each protein. Thus a human monoclonal anti-idiotypic antibody generated by a cancer patient is able to show both amino acid and structural homology with the complement regulatory protein CD55. These findings help identify the mechanism by which a human anti-idiotypic antibody is able to mimic a tumor-associated antigen and stimulate anti-tumor B and T cell responses.
Authors	L Spendlove, L Li, V Potter, D Christiansen, B E Loveland, L G Durrant
Journal	European journal of immunology (Eur J Immunol) Vol. 30 Issue 10 Pg. 2944-53 (Oct 2000) ISSN: 0014-2980 [Print] Germany
PMID	11069077 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Adjuvants, Immunologic Antibodies, Anti-Idiotypic Antibodies, Monoclonal Antibodies, Neoplasm Antigens, CD Antigens, Neoplasm CD46 protein, human CD55 Antigens Immune Sera Immunoglobulin Variable Region Mcp protein, mouse Membrane Cofactor Protein Membrane Glycoproteins Peptide Fragments Recombinant Fusion Proteins
Topics	Adenocarcinoma (diagnostic imaging, immunology, secondary, therapy) Adjuvants, Immunologic (chemistry, therapeutic use) Amino Acid Sequence Animals Antibodies, Anti-Idiotypic (chemistry, genetics, therapeutic use) Antibodies, Monoclonal (chemistry, genetics, immunology) Antibodies, Neoplasm (biosynthesis, immunology) Antigen-Antibody Reactions Antigens, CD (chemistry) Antigens, Neoplasm (chemistry, genetics, immunology) Binding Sites, Antibody CD55 Antigens (chemistry, genetics, immunology) CHO Cells Cloning, Molecular Colorectal Neoplasms (immunology, therapy) Cricetinae Genes, Immunoglobulin Humans Immune Sera (immunology) Immunity, Cellular Immunoglobulin Variable Region (genetics) Liver Neoplasms (diagnostic imaging, secondary) Membrane Cofactor Protein Membrane Glycoproteins (chemistry) Mice Mice, Inbred BALB C Models, Molecular Molecular Mimicry Molecular Sequence Data Peptide Fragments (chemistry) Protein Conformation Protein Structure, Tertiary Radioimmunodetection Recombinant Fusion Proteins (chemistry, immunology) Sequence Alignment Sequence Homology, Amino Acid Transfection

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!