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

Authors: Bolognesi, Andrea1; Tazzari, Pier Luigi2; Olivieri, Fabiola1; Polito, Letizia1; Lemoli, Roberto3; Terenzi, Adelmo4; Pasqualucci, Laura4; Falini, Brunangelo4; Stirpe, Fiorenzo1

Source: British Journal of Haematology, Volume 101, Number 1, April 1998 , pp. 179-188(10)

Publisher: Blackwell Publishing

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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 × 10−15 to 7.6 × 10−11 Mas RIP, and IC90 (concentration causing 90% inhibition) ranging from 5 × 10−14 to 5 × 10−8 M, with no effect on a CD22-negative HL60 cell line at the highest concentration tested (5 × 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 × 10−6), when 60% of the animals remained tumour-free.

Keywords: immunotoxins; ribosome-inactivating proteins; non-Hodgkin's B lymphomas; CD22 antigen; apoptosis

Document Type: Original article

DOI: 10.1046/j.1365-2141.1998.00665.x

Affiliations: 1: Dipartimento di Patologia Sperimentale, Università di Bologna, 2: Servizio di Immunoematologia e Trasfusionale, Policlinico S. Orsola, Bologna, 3: Istituto di Ematologia `L. e A. Seràgnoli', Università di Bologna, 4: Istituto di Ematologia, Università di Perugia, Italy

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