Targeting of type 1 ribosome-inactivating proteins to CD30+ or CD25+ hematologic neoplasias by bispecific antibodies.
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.
Sforzini
S
S
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Bolognesi
A
A
Meazza
R
R
Marciano
S
S
Tazzari
P L
PL
Stein
H
H
Stirpe
F
F
Ferrini
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000378:metabolism*; D002051:Burkitt Lymphoma / Q000473:pathology; D004357:Drug Synergism; D006689:Hodgkin Disease / Q000473:pathology*; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage*; D017730:Ki-1 Antigen / Q000378:metabolism*; D051379:Mice; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000008:administration & dosage* / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000922:Immunotoxins; D017730:Ki-1 Antigen; D010940:Plant Proteins; D015375:Receptors, Interleukin-2; D054789:Ribosome Inactivating Proteins, Type 1; C025674:GEL protein, Gelonium multiflorum; D009699:N-Glycosyl Hydrolases; D000076985:Saporins