Linked Life Data

9679766

Source:http://linkedlifedata.com/resource/pubmed/id/9679766

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1998-7-30
pubmed:abstractText
We have developed a new modular affinity system for the 2-step delivery of functional molecules to target cells. The system is based on the tautomer-specific monoclonal antibody (MAb) EM-6-47, which binds to 3- and 3,8-substituted adenines with high affinity (Ka > 10(9) l/mol) without cross-reacting with naturally occurring purine derivatives. This MAb serves as the hapten-specific fusion partner to produce bispecific MAbs (bs-MAbs) recognizing a target cell antigen and a low-m.w. hapten as carrier molecule for, e.g., radionuclides. Either the C-8 or the N-3 position of adenines can be used for conjugation with effector molecules; the remaining position may be substituted with different moieties to modulate the pharmacokinetics of the haptens. Different 3- and 3,8-substituted adenines conjugated to the chelates DOTA and DTPA or to the drug daunomycin were synthesized. Adenine-chelate derivatives were efficiently labeled with (111)In and 90Y, while high-affinity binding of 3-substituted adenines to MAb EM-6-47 remained almost unaffected by the conjugation to radiochelates. To confirm the validity of the delivery system, a prototype bs-MAb, EM-168-47, was generated by somatic cell fusion of MAb EM-6-47 and MAb EM-168-2, the latter recognizing a surface antigen on canine hematopoietic cells. Two-step targeting assays in vitro verified the bs-MAb-mediated, dose-dependent delivery of (111)In-labeled adenine-chelate derivatives to myeloid cells. This system represents a powerful tool for new pre-targeting approaches relying on bs-MAbs and low-m.w. haptens. Suitable cellular antigens can be targeted by fusing the appropriate MAbs with hapten-specific MAb EM-6-47, and tailor-made 3-substituted adenines may be labeled with diagnostic or therapeutic radionuclides, cytotoxic drugs or other functional molecules.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
77
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
610-9
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
New modular delivery system for diagnostic and therapeutic pre-targeting using tautomer-specific monoclonal antibody EM-6-47 and 3-substituted adenines.
pubmed:affiliation
Institute of Cell Biology (Cancer Research), Center of Cancer Research and Cancer Therapy, University of Essen Medical School, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't