Linked Life Data

7885077

Source:http://linkedlifedata.com/resource/pubmed/id/7885077

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1995-4-13
pubmed:abstractText
Several recent reports have demonstrated that anticancer drugs can be generated site-selectively at solid tumors by monoclonal antibody-enzyme conjugates targeted to antigens on tumor cell surfaces. The first step in this drug targeting approach involves the delivery of the enzyme conjugate to a tumor cell population. After the conjugate has localized within the tumor and cleared from non-target tissues, a relatively non-cytotoxic drug precursor (prodrug) is administered. Upon contact with the targeted enzyme, the prodrug is converted into a toxic drug. Several examples are presented to illustrate this targeting strategy. Monoclonal antibody-beta-lactamase conjugates have been developed to activate a panel of anticancer prodrugs that are mechanistically dissimilar. The antitumor activities of the monoclonal antibody-beta-lactamase conjugate/prodrug combinations exceed those obtained by systemic drug administration, and are immunologically specific. In another example involving targeted cytosine deaminase for the generation of 5-fluorouracil, it is shown that as much as 17 times more drug can be delivered within a tumor compared to when 5-fluorouracil is administered alone. The method of using targeted enzymes for prodrug activation can be extended to include prodrugs that release very potent drugs, such as palytoxin, a marine natural product, and to treat cells that have the multidrug resistance phenotype. Some of the requirements for successful therapy with this approach for cancer therapy are discussed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0379-0355
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
505-12
pubmed:dateRevised
2005-11-16
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Selective activation of anticancer prodrugs by monoclonal antibody-enzyme conjugates.
pubmed:affiliation
Bristol Myers Squibb Pharmaceutical Research Institute, Seattle, Washington.
pubmed:publicationType
Journal Article, Review