Linked Life Data

18922911

Source:http://linkedlifedata.com/resource/pubmed/id/18922911

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2008-10-16
pubmed:abstractText
Multivalent antibodies, either monospecific or bispecific, may improve the efficacy of current therapeutic interventions involving a single monoclonal antibody (mAb). We have applied the Dock-and-Lock (DNL) method, a new platform technology for the site-specific and covalent assembly of modular components into stably tethered complexes of defined composition, to prepare a hexavalent, anti-CD20 antibody, designated Hex-hA20, which comprises six Fabs with one Fc. We show that Hex-hA20 retains the binding activity of all six Fabs, associates with CD20 in lipid rafts, affects antibody-dependent cell-mediated cytotoxicity, but not complement-dependent cytotoxicity, and inhibits proliferation of Daudi, Raji, and Ramos cells in vitro at subnanomolar concentrations without the need for a cross-linking antibody. In addition, Hex-hA20 induces strong homotypical adhesion and is inefficient in stimulating calcium mobilization. Thus, Hex-hA20 exhibits biological properties attributable to both type I and type II anti-CD20 mAbs, as exemplified by rituximab and tositumomab, respectively. Although Hex-hA20 has a short serum half-life, it shows antitumor efficacy in tumor-bearing mice comparable with veltuzumab at equivalent doses. The versatile DNL method was also applied to generate two other multivalent anti-CD20 antibodies without the Fc region, Tri-hA20 and Tetra-hA20, comprising three and four Fabs of veltuzumab, respectively. Similar to Hex-hA20, these were purified to near homogeneity and shown to have potent antiproliferative activity in vitro, thus indicating the need for clustering three or more CD20 molecules on the cell surface to induce growth inhibition.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8384-92
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Novel designs of multivalent anti-CD20 humanized antibodies as improved lymphoma therapeutics.
pubmed:affiliation
IBC Pharmaceuticals, Inc, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural