Linked Life Data

16814387

Source:http://linkedlifedata.com/resource/pubmed/id/16814387

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-9-26
pubmed:abstractText
Epratuzumab is a humanized anti-CD22 monoclonal antibody currently in clinical trials for treatment of non-Hodgkin lymphoma (NHL) and certain autoimmune diseases. Here we report the results of investigations of epratuzumab's mode of action in comparison to and in combination with the anti-CD20 mAb, rituximab. In vitro cell growth inhibition, induction of apoptosis, and the ability of the mAbs to mediate complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) were evaluated. We also investigated the potential activity of epratuzumab in the regulation of B-cell antigen receptor (BCR) activation. Epratuzumab and rituximab displayed very distinct modes of action; epratuzumab acts as an immunomodulatory agent, while rituximab is an acutely cytotoxic therapeutic antibody. Epratuzumab has distinct effects on cell growth from rituximab. For example, rituximab+anti-human IgG Fcgamma yielded marked inhibition of proliferation in human NHL cell lines, while epratuzumab had little or no effect in this assay. However, when cells were immobilized and stimulated with anti-IgM, epratuzumab, but not rituximab, caused a significant antiproliferative effect. Unlike rituximab, no CDC could be detected, and ADCC was modest but significant with epratuzumab. Importantly, combining rituximab and epratuzumab did not decrease rituximab's ability to induce apoptosis, CDC, and ADCC. In fact, the combination is more effective than rituximab alone in inhibiting proliferation of Daudi Burkitt lymphoma cells in the presence of second antibody, and at least equally effective to rituximab in the absence of crosslinking. These observations suggest that it may be possible to enhance clinical efficacy by combination therapy comprised of anti-CD20 and anti-CD22 mAbs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0161-5890
pubmed:author
pubmed:issnType
Print
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1331-41
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Epratuzumab, a CD22-targeting recombinant humanized antibody with a different mode of action from rituximab.
pubmed:affiliation
Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
pubmed:publicationType
Journal Article, Comparative Study