Linked Life Data

16151407

Source:http://linkedlifedata.com/resource/pubmed/id/16151407

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2005-9-9
pubmed:abstractText
Immunoconjugates--monoclonal antibodies (mAbs) coupled to highly toxic agents, including radioisotopes and toxic drugs (ineffective when administered systemically alone)--are becoming a significant component of anticancer treatments. By combining the exquisite targeting specificity of mAbs with the enhanced tumor-killing power of toxic effector molecules, immunoconjugates permit sensitive discrimination between target and normal tissue, resulting in fewer toxic side effects than most conventional chemotherapeutic drugs. Two radioimmunoconjugates, ibritumomab tiuxetan (Zevalin) and tositumomab-131I (Bexxar), and one drug conjugate, gemtuzumab ozogamicin (Mylotarg), are now on the market. For the next generation of immunoconjugates, advances in protein engineering will permit greater control of mAb targeting, clearance and pharmacokinetics, resulting in significantly improved delivery to tumors of radioisotopes and potent anticancer drugs. Pre-targeting strategies, which separate the two functions of antibody-based localization and delivery or generation of the toxic agent into two steps, also promise to afford superior tumor targeting and therapeutic efficacy. Several challenges in optimizing immunoconjugates remain, however, including poor intratumoral mAb uptake, normal tissue conjugate exposure and issues surrounding drug potency and conditional release from mAb carriers. Nonetheless, highly promising results from preclinical models will continue to drive the clinical development of this therapeutic class.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1087-0156
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1137-46
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:16151407-Aminoglycosides, pubmed-meshheading:16151407-Animals, pubmed-meshheading:16151407-Antibodies, pubmed-meshheading:16151407-Antibodies, Monoclonal, pubmed-meshheading:16151407-Antibodies, Monoclonal, Humanized, pubmed-meshheading:16151407-Biotechnology, pubmed-meshheading:16151407-Biotinylation, pubmed-meshheading:16151407-Humans, pubmed-meshheading:16151407-Immunoconjugates, pubmed-meshheading:16151407-Immunoglobulin Fragments, pubmed-meshheading:16151407-Immunotherapy, pubmed-meshheading:16151407-Models, Chemical, pubmed-meshheading:16151407-Neoplasms, pubmed-meshheading:16151407-Prodrugs, pubmed-meshheading:16151407-Protein Engineering, pubmed-meshheading:16151407-Radioimmunotherapy, pubmed-meshheading:16151407-Radioisotopes, pubmed-meshheading:16151407-Time Factors
pubmed:year
2005
pubmed:articleTitle
Arming antibodies: prospects and challenges for immunoconjugates.
pubmed:affiliation
Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, Box 951770, 700 Westwood Plaza, Los Angeles, California 90095, USA. awu@mednet.ucla.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Review, Research Support, N.I.H., Extramural