Evaluation of immunotoxins containing single-chain ribosome-inactivating proteins and an anti-CD22 monoclonal antibody (OM124): in vitro and in vivo studies

Br J Haematol. 1998 Apr;101(1):179-88. doi: 10.1046/j.1365-2141.1998.00665.x.

Abstract

Immunotoxins were prepared with three ribosome-inactivating proteins (RIP), momordin, pokeweed antiviral protein from seeds (PAP-S) and saporin-S6, linked to the anti-CD22 monoclonal antibody OM124. These immunotoxins inhibited protein synthesis by CD22-expressing cell lines Daudi, EHM, BJAB, Raji and BM21 with IC50 (concentration causing 50% inhibition) ranging from < 5 x 10(-15) to 7.6 x 10(-11) M as RIP, and IC90 (concentration causing 90% inhibition) ranging from 5 x 10(-14) to 5 x 10(-8)M, with no effect on a CD22-negative HL60 cell line at the highest concentration tested (5 x 10[-8] M). Apoptosis was induced in sensitive cells. The formation of bone marrow colonies was inhibited by no more than 40% by the immunotoxins at concentrations up to 10(-9) M. Treatment with the immunotoxins, alone or in combination, significantly extended the survival time of mice bearing transplanted Daudi cells. A treatment with cyclophosphamide and OM124/saporin immunotoxin was particularly effective in SCID mice transplanted with a low number of cells (3 x 10[-6]), when 60% of the animals remained tumour-free.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antigens, CD / immunology*
  • Antigens, Differentiation, B-Lymphocyte / immunology*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Bone Marrow Cells / pathology
  • Cell Adhesion Molecules*
  • Cell Survival
  • Immunotoxins / pharmacology*
  • Lectins*
  • Lymphoma, B-Cell / pathology
  • Mice
  • N-Glycosyl Hydrolases*
  • Plant Proteins / pharmacology*
  • Protein Synthesis Inhibitors / pharmacology
  • Ribosome Inactivating Proteins, Type 1
  • Ribosome Inactivating Proteins, Type 2
  • Saporins
  • Sialic Acid Binding Ig-like Lectin 2
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • Antineoplastic Agents, Phytogenic
  • Cd22 protein, mouse
  • Cell Adhesion Molecules
  • Immunotoxins
  • Lectins
  • Plant Proteins
  • Protein Synthesis Inhibitors
  • Ribosome Inactivating Proteins, Type 1
  • Ribosome Inactivating Proteins, Type 2
  • Sialic Acid Binding Ig-like Lectin 2
  • N-Glycosyl Hydrolases
  • Saporins
  • pokeweed antiviral protein