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Targeting of type 1 ribosome-inactivating proteins to CD30+ or CD25+ hematologic neoplasias by bispecific antibodies.

Abstract
In this study, we compared the ability of different bispecific monoclonal antibodies (BsmAb) and immunotoxins to deliver the type 1 ribosome-inactivating proteins (RIP) saporin and gelonin through the CD25 or CD30 target molecules to Hodgkin's lymphoma cells. An anti-CD25/antisaporin and an anti-CD30/antisaporin BsmAb enhanced the toxicity of the relevant RIP against the CD25+CD30+ L540 Hodgkin's lymphoma cell line, although targeting by anti-CD30 BsmAb appeared eight times more efficient. Two anti-CD30/antigelonin BsmAb, reacting with different epitopes of the gelonin molecule, were able to enhance gelonin toxicity against L540 cells and had a synergistic effect when used in combination. Among CD25-CD30+ Hodgkin's lymphoma lines, which were resistant to targeting by anti-CD25/saporin BsmAb, one (L428) was sensitive to both gelonin and saporin delivered by anti-CD30 BsmAb. Another CD25-CD30+ cell line (COLE) was completely resistant to the toxic effect of gelonin targeted by the two synergistic BsmAb, as well as to an anti-CD30/gelonin immunotoxin. However, these cells were partially sensitive to saporin delivered by an anti-CD30/anti-saporin BsmAb, and they were efficiently killed by an anti-CD30/saporin immunotoxin. These results indicate that heterogeneity in the sensitivity to certain RIP, such as gelonin, exists among tumor cells of the same histotype.
AuthorsS Sforzini, A Bolognesi, R Meazza, S Marciano, P L Tazzari, H Stein, F Stirpe, S Ferrini
JournalJournal of hematotherapy (J Hematother) Vol. 4 Issue 5 Pg. 429-32 (Oct 1995) ISSN: 1061-6128 [Print] United States
PMID8581380 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Immunotoxins
  • Ki-1 Antigen
  • Plant Proteins
  • Receptors, Interleukin-2
  • Ribosome Inactivating Proteins, Type 1
  • GEL protein, Gelonium multiflorum
  • N-Glycosyl Hydrolases
  • Saporins
Topics
  • Animals
  • Antibodies, Monoclonal (administration & dosage, immunology)
  • Antibody Specificity
  • Antigens, Neoplasm (metabolism)
  • Burkitt Lymphoma (pathology)
  • Drug Synergism
  • Hodgkin Disease (pathology)
  • Humans
  • Immunotoxins (administration & dosage)
  • Ki-1 Antigen (metabolism)
  • Mice
  • N-Glycosyl Hydrolases
  • Plant Proteins (administration & dosage, immunology)
  • Receptors, Interleukin-2 (metabolism)
  • Ribosome Inactivating Proteins, Type 1
  • Saporins
  • Tumor Cells, Cultured

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