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

Andrea Bolognesi, Pier Luigi Tazzari, Fabiola Olivieri, Letizia Polito, Roberto Lemoli, Adelmo Terenzi, Laura Pasqualucci, Brunangelo Falini, Fiorenzo Stirpe

Research output: Contribution to journalArticle

34 Citations (Scopus)

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 10-8M, 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 60% 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.

Original languageEnglish
Pages (from-to)179-188
Number of pages10
JournalBritish Journal of Haematology
Volume101
Issue number1
DOIs
Publication statusPublished - 1998

Fingerprint

Ribosome Inactivating Proteins
Immunotoxins
Monoclonal Antibodies
S 6
Cell Line
SCID Mice
HL-60 Cells
Cyclophosphamide
Inhibitory Concentration 50
Seeds
Cell Count
Bone Marrow
In Vitro Techniques
Apoptosis
Neoplasms
Proteins

Keywords

  • Apoptosis
  • CD22 antigen
  • Immunotoxins
  • Non-Hodgkin's B lymphomas
  • Ribosome-inactivating proteins

ASJC Scopus subject areas

  • Hematology

Cite this

Evaluation of immunotoxins containing single-chain ribosome- inactivating proteins and an anti-CD22 monoclonal antibody (OM124) : In vitro and in vivo studies. / Bolognesi, Andrea; Tazzari, Pier Luigi; Olivieri, Fabiola; Polito, Letizia; Lemoli, Roberto; Terenzi, Adelmo; Pasqualucci, Laura; Falini, Brunangelo; Stirpe, Fiorenzo.

In: British Journal of Haematology, Vol. 101, No. 1, 1998, p. 179-188.

Research output: Contribution to journalArticle

Bolognesi, Andrea ; Tazzari, Pier Luigi ; Olivieri, Fabiola ; Polito, Letizia ; Lemoli, Roberto ; Terenzi, Adelmo ; Pasqualucci, Laura ; Falini, Brunangelo ; Stirpe, Fiorenzo. / Evaluation of immunotoxins containing single-chain ribosome- inactivating proteins and an anti-CD22 monoclonal antibody (OM124) : In vitro and in vivo studies. In: British Journal of Haematology. 1998 ; Vol. 101, No. 1. pp. 179-188.
@article{e0c0c546db8a44c09712fd820aebc9e8,
title = "Evaluation of immunotoxins containing single-chain ribosome- inactivating proteins and an anti-CD22 monoclonal antibody (OM124): In vitro and in vivo studies",
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 10-8M, 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 60{\%} 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.",
keywords = "Apoptosis, CD22 antigen, Immunotoxins, Non-Hodgkin's B lymphomas, Ribosome-inactivating proteins",
author = "Andrea Bolognesi and Tazzari, {Pier Luigi} and Fabiola Olivieri and Letizia Polito and Roberto Lemoli and Adelmo Terenzi and Laura Pasqualucci and Brunangelo Falini and Fiorenzo Stirpe",
year = "1998",
doi = "10.1046/j.1365-2141.1998.00665.x",
language = "English",
volume = "101",
pages = "179--188",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "John Wiley & Sons, Ltd (10.1111)",
number = "1",

}

TY - JOUR

T1 - Evaluation of immunotoxins containing single-chain ribosome- inactivating proteins and an anti-CD22 monoclonal antibody (OM124)

T2 - In vitro and in vivo studies

AU - Bolognesi, Andrea

AU - Tazzari, Pier Luigi

AU - Olivieri, Fabiola

AU - Polito, Letizia

AU - Lemoli, Roberto

AU - Terenzi, Adelmo

AU - Pasqualucci, Laura

AU - Falini, Brunangelo

AU - Stirpe, Fiorenzo

PY - 1998

Y1 - 1998

N2 - 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 10-8M, 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 60% 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.

AB - 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 10-8M, 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 60% 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.

KW - Apoptosis

KW - CD22 antigen

KW - Immunotoxins

KW - Non-Hodgkin's B lymphomas

KW - Ribosome-inactivating proteins

UR - http://www.scopus.com/inward/record.url?scp=0031980763&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031980763&partnerID=8YFLogxK

U2 - 10.1046/j.1365-2141.1998.00665.x

DO - 10.1046/j.1365-2141.1998.00665.x

M3 - Article

C2 - 9576199

AN - SCOPUS:0031980763

VL - 101

SP - 179

EP - 188

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 1

ER -