Linked Life Data

2152774

Source:http://linkedlifedata.com/resource/pubmed/id/2152774

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1990-1-25
pubmed:abstractText
Five monoclonal CD30 antibodies and two Fab' fragments were linked to deglycosylated ricin A chain (dgA), and their potential as immunotoxins for the treatment of Hodgkin's disease was evaluated. Cross-blocking experiments demonstrated that HRS-1, HRS-3, HRS-4, and Ber-H2 recognize the same epitope on the CD30 antigen and that Ki-1 binds to a different epitope. Scatchard analyses showed that HRS-3, HRS-4, and Ber-H2 bound strongly to L540 Hodgkin cells (Kd 15, 7, and 14 nM, respectively), whereas HRS-1 and Ki-1 bound more weakly (Kd 160 and 380 nM, respectively). The different affinities of the antibodies correlated closely with their cytotoxic potency as immunotoxins. HRS-3.dgA, HRS-4.dgA, and Ber-H2.dgA inhibited the protein synthesis of L540 cells by 50% at concentrations of 0.9-2.0 x 10(-10) M, whereas HRS-1.dgA and Ki-1.dgA were about 100 times less potent with 50% inhibitory concentrations of 0.8-1.0 x 10(-8) M. The most effective immunotoxins, HRS-3.dgA and HRS-4.dgA, were only 15 times less toxic than ricin itself. HRS-3 Fab'.dgA and HRS-4 Fab'.dgA were 7.8 and 3 times less potent than their IgG.dgA counterparts with 50% inhibitory concentrations of 7 x 10(-10) and 3 x 10(-10) M, respectively. Staining of human tissues revealed an unexpected cross-reactivity of HRS-4 with pancreatic cells of malignant and nonmalignant origin. HRS-1, HRS-3, Ber-H2, and Ki-1 showed very little cross-reactivity with any normal human tissues. It is concluded that HRS-3.dgA and HRS-3 Fab'.dgA are the immunotoxins of choice for in vivo therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
84-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:2152774-Antibodies, Monoclonal, pubmed-meshheading:2152774-Antigen-Antibody Complex, pubmed-meshheading:2152774-Antigens, CD, pubmed-meshheading:2152774-Antigens, CD30, pubmed-meshheading:2152774-Antigens, Differentiation, pubmed-meshheading:2152774-Antigens, Neoplasm, pubmed-meshheading:2152774-Cell Line, pubmed-meshheading:2152774-Cell Survival, pubmed-meshheading:2152774-Cross Reactions, pubmed-meshheading:2152774-Female, pubmed-meshheading:2152774-Hodgkin Disease, pubmed-meshheading:2152774-Humans, pubmed-meshheading:2152774-Immunoglobulin Fab Fragments, pubmed-meshheading:2152774-Immunoglobulin G, pubmed-meshheading:2152774-Immunotoxins, pubmed-meshheading:2152774-Iodine Radioisotopes, pubmed-meshheading:2152774-Neoplasms, pubmed-meshheading:2152774-Ricin, pubmed-meshheading:2152774-Tumor Cells, Cultured
pubmed:year
1990
pubmed:articleTitle
Evaluation of ricin A chain-containing immunotoxins directed against the CD30 antigen as potential reagents for the treatment of Hodgkin's disease.
pubmed:affiliation
Drug Targeting Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't