Evaluation of immunotoxins containing single-chain ribosome-inactivating proteins and an anti-CD22 monoclonal antibody (OM124): in vitro and in vivo studies
| Autor: | A, Bolognesi, P L, Tazzari, F, Olivieri, L, Polito, R, Lemoli, A, Terenzi, L, Pasqualucci, B, Falini, F, Stirpe |
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| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Lymphoma
B-Cell Animals Antibodies Monoclonal Antigens CD Antigens CD22 Antigens Differentiation B-Lymphocyte Antineoplastic Agents Phytogenic Apoptosis Bone Marrow Cells Cell Adhesion Molecules Cell Survival Immunotoxins Lectins Lymphoma B-Cell Mice N-Glycosyl Hydrolases Plant Proteins Protein Synthesis Inhibitors Ribosome Inactivating Proteins Type 1 Ribosome Inactivating Proteins Type 2 Tumor Cells Cultured Lymphoma Cell Survival Sialic Acid Binding Ig-like Lectin 2 Ribosome Inactivating Proteins Antineoplastic Agents Apoptosis Bone Marrow Cells Antibodies Mice Antigens CD Phytogenic Lectins Monoclonal Tumor Cells Cultured Animals Antigens CD22 N-Glycosyl Hydrolases Plant Proteins Protein Synthesis Inhibitors Immunotoxins B-Lymphocyte B-Cell Antibodies Monoclonal Antineoplastic Agents Phytogenic Saporins CD Tumor Cells Antigens Differentiation B-Lymphocyte Ribosome Inactivating Proteins Type 2 Ribosome Inactivating Proteins Type 1 Cell Adhesion Molecules Type 2 Type 1 |
| Popis: | 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 from5 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. |
| Databáze: | OpenAIRE |
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