Decay accelerating factor (CD55): a target for cancer vaccines?
The 791Tgp72 antigen has been used successfully as a target for tumor imaging and T-cell immunotherapy. We have characterized this antigen using the monoclonal antibody 791T/36 as a 72/66 kDa doublet. NH2-terminal protein sequencing of the two bands revealed identity with the complement regulatory protein CD55. Antibodies recognizing different domains of CD55 were also shown to bind to the purified 791Tgp72, although sequence analysis of the cDNA cloned from 791T tumor cells showed 100% homology with CD55 and transfection of the cDNA into antigen-negative CHO cells resulted in binding of 791T/36. This identifies the tumor antigen 791Tgp72 as CD55. This protein protects cells from complement attack; however, it can also transduce signals in lymphocytes and is a ligand for CD97, expressed by activated T cells. These results suggest that CD55 plays a role in signaling between the innate and adaptive immune responses. It is therefore a very intriguing target, because absence of the molecule makes the tumor cells susceptible to complement, whereas protective overexpression results in the antigen being a target for T-cell immunotherapy.
Spendlove
I
I
Cancer Research Campaign Academic Unit of Clinical Oncology, University of Nottingham, City Hospital, United Kingdom. Ian.Spendlove@Nottingham.ac.uk
Li
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L
Carmichael
J
J
Durrant
L G
LG
D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001859:Bone Neoplasms / Q000276:immunology / Q000473:pathology*; D018958:CD55 Antigens / Q000276:immunology*; D016466:CHO Cells; D019496:Cancer Vaccines; D003165:Complement System Proteins / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000276:immunology*; D012516:Osteosarcoma / Q000276:immunology / Q000473:pathology*; D017421:Sequence Analysis; D013601:T-Lymphocytes / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D018958:CD55 Antigens; D019496:Cancer Vaccines; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D003165:Complement System Proteins