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

Sabrina Sforzini, Daniela De Totero, Alessia Gaggero, Rodolfo Ippoliti, Martin J. Glennie, Silvana Canevari, Harald Stein, Silvano Ferrini

Research output: Contribution to journalArticle

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 10-9M CD30 x sap1 bimAb the IC50 was 2.75 x 10-11M, whereas with CD30 x sap2 bimAb the IC50 was 6.5 x 10-11 and CD25 x sap1 bimAb displayed an IC50 of 3 x 10-11M (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/antisaporin 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.

Original languageEnglish
Pages (from-to)1061-1068
Number of pages8
JournalBritish Journal of Haematology
Volume102
Issue number4
DOIs
Publication statusPublished - 1998

Keywords

  • Bispecific monoclonal antibodies
  • CD25
  • CD30
  • Hodgkin's lymphoma
  • Saporin

ASJC Scopus subject areas

  • Hematology

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    Sforzini, S., De Totero, D., Gaggero, A., Ippoliti, R., Glennie, M. J., Canevari, S., Stein, H., & Ferrini, S. (1998). Targeting of saporin to Hodgkin's lymphoma cells by anti-CD30 and anti- CD25 bispecific antibodies. British Journal of Haematology, 102(4), 1061-1068. https://doi.org/10.1046/j.1365-2141.1998.00859.x