Linked Life Data

18502181

Source:http://linkedlifedata.com/resource/pubmed/id/18502181

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-7-15
pubmed:abstractText
Complement-dependent cytotoxicity (CDC) is thought to be one of the most important mechanisms of action of therapeutic monoclonal antibodies (mAbs). The decay-accelerating factor (DAF) overexpressed in certain tumors limits the CDC effect of the therapeutic anticancer antibodies. The use of DAF blocking antibodies targeted specifically at cancer cells in combination with immunotherapeutic mAbs of cancer may improve the therapeutic effect in cancer patients. In this study, the lysis of Raji cells mediated by CDC was determined after blocking DAF function by anti-DAF polyclonal antibody and 3 mAbs (DG3, DG9, DA11) prepared in our laboratory, respectively, in the presence of the anti-CD20 chimeric mAb rituximab. The binding domains of the three anti-DAF mAbs were identified using yeast surface display technique, and the mimic epitopes of mAb DG3 were screened from a random phage-display nonapeptide library. The results showed that blocking DAF function by anti-DAF polyclonal antibody enhanced complement-mediated killing of Raji cells. Among the 3 mAbs against DAF, only DG3 was found to be able to remarkably enhance the CDC effect of the therapeutic mAb rituximab. DG3 bound to the third short consensus repeat (SCR) of DAF. Binding of DG3 to immobilized DAF was inhibited by mimic epitope peptides screened from the peptide library. Our results suggest that a higher level of DAF expressed by certain tumor cells is significant to abolish the CDC effect of therapeutic anticancer antibodies, and mAbs binding to SCR3 can enhance the complement-mediated killing of Raji cells. It is of significance to identify the DAF epitopes required in inhibiting CDC not only for better understanding of the relationship between the structure and function of DAF, but also for designing and developing anti-DAF mAbs capable of enhancing CDC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1521-7035
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
155-63
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:18502181-Antibodies, Monoclonal, pubmed-meshheading:18502181-Antibodies, Monoclonal, Murine-Derived, pubmed-meshheading:18502181-Antibody Specificity, pubmed-meshheading:18502181-Antigens, CD20, pubmed-meshheading:18502181-Antigens, CD55, pubmed-meshheading:18502181-Antineoplastic Agents, pubmed-meshheading:18502181-Cell Death, pubmed-meshheading:18502181-Cell Line, Tumor, pubmed-meshheading:18502181-Complement Activation, pubmed-meshheading:18502181-Complement System Proteins, pubmed-meshheading:18502181-Cytotoxicity, Immunologic, pubmed-meshheading:18502181-Cytotoxicity Tests, Immunologic, pubmed-meshheading:18502181-Dose-Response Relationship, Immunologic, pubmed-meshheading:18502181-Epitope Mapping, pubmed-meshheading:18502181-Epitopes, pubmed-meshheading:18502181-Humans
pubmed:year
2008
pubmed:articleTitle
Mapping of binding epitopes of a human decay-accelerating factor monoclonal antibody capable of enhancing rituximab-mediated complement-dependent cytotoxicity.
pubmed:affiliation
Institute of Immunology, Third Military Medical University, District Shapingba, Chongqing 400038, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't