Targeting of saporin to Hodgkin's lymphoma cells by anti-CD30 and anti-CD25 bispecific antibodies.

Abstract

CD25 and CD30 represent suitable target molecules for bispecific antibody (bimAb)-driven toxin delivery to lymphoid tumour cells. We describe two new anti-CD30/anti-saporin bimAbs (termed CD30 x sap1 and CD30 x sap2), produced by hybrid hybridomas, which react against non-cross-reactive epitopes of the saporin molecule, and compared their effect with a bimAb reacting with saporin and with CD25 (CD25 x sap1). In a protein synthesis inhibition assay these bimAbs were able to enhance saporin toxicity (IC50 = 8.5 x 10(-9) M in the absence of mAbs) with a similar activity: in the presence of 10(-9) M CD30 x sap1 bimAb the IC50 was 2.75 x 10(-11) M, whereas with CD30 x sap2 bimAb the IC50 was 6.5 x 10(-11) M and CD25 x sap1 bimAb displayed an IC50 of 3 x 10(-11) M (as saporin). The combined use of the two anti-CD30 bimAbs further increased cytotoxicity by 100-fold, resulting in an IC50 of 1.9 x 10(-13) M. A slightly less efficient improvement was obtained by combining the CD25 x sap1 bimAb with the CD30 x sap2 bimAb directed against a different toxin epitope (saporin IC50 to 7 x 10(-13) M). In contrast, no synergistic effect was observed using the combination of the anti-CD25 bimAb with the anti-CD30 bimAb reacting with the same epitope of saporin (IC50 = 4.5 x 10(-11) M). Analysis of FITC-saporin binding to L540 cells by flow cytometry demonstrated that the appropriate combinations of the two anti-CD30/anti-saporin bimAbs or of the anti-CD30/anti-saporin and anti-CD25/anti-saporin bimAbs had a cooperative effect on the binding of the ribosome-inactivating protein (RIP) to the cells, when compared with single bimAbs.

• Authors: S Sforzini, D de Totero, A Gaggero, R Ippoliti, M J Glennie, S Canevari, H Stein, S Ferrini
• Journal: British journal of haematology (Br J Haematol) Vol. 102 Issue 4 Pg. 1061-8 (Sep 1998) ISSN: 0007-1048 [Print] England
• PMID: 9734659 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Bispecific
• Antigens, Neoplasm
• Antineoplastic Agents, Phytogenic
• Immunotoxins
• Ki-1 Antigen
• Neoplasm Proteins
• Plant Proteins
• Receptors, Interleukin-2
• Ribosome Inactivating Proteins, Type 1
• N-Glycosyl Hydrolases
• Saporins

Topics

• Antibodies, Bispecific (biosynthesis, immunology)
• Antigens, Neoplasm (immunology)
• Antineoplastic Agents, Phytogenic (immunology, pharmacokinetics, pharmacology)
• Cell Death (drug effects)
• Dose-Response Relationship, Drug
• Hodgkin Disease (immunology, metabolism)
• Humans
• Hybridomas (immunology)
• Immunotoxins (pharmacokinetics)
• Ki-1 Antigen (immunology)
• N-Glycosyl Hydrolases
• Neoplasm Proteins (biosynthesis)
• Plant Proteins (immunology, pharmacokinetics, pharmacology)
• Receptors, Interleukin-2 (immunology)
• Ribosome Inactivating Proteins, Type 1
• Saporins
• Tumor Cells, Cultured