Evaluation of immunotoxins containing single-chain ribosome-inactivating proteins and an anti-CD22 monoclonal antibody (OM124): in vitro and in vivo studies.
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.
Bolognesi
A
A
Dipartimento di Patologia Sperimentale, Università di Bologna, Italy.
Tazzari
P L
PL
Olivieri
F
F
Polito
L
L
Lemoli
R
R
Terenzi
A
A
Pasqualucci
L
L
Falini
B
B
Stirpe
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000473:pathology; D015815:Cell Adhesion Molecules; D002470:Cell Survival; D000922:Immunotoxins / Q000494:pharmacology*; D037102:Lectins; D016393:Lymphoma, B-Cell / Q000473:pathology; D051379:Mice; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D054789:Ribosome Inactivating Proteins, Type 1; D054790:Ribosome Inactivating Proteins, Type 2; D000076985:Saporins; D051918:Sialic Acid Binding Ig-like Lectin 2; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000972:Antineoplastic Agents, Phytogenic; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D000922:Immunotoxins; D037102:Lectins; D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; D054789:Ribosome Inactivating Proteins, Type 1; D054790:Ribosome Inactivating Proteins, Type 2; D051918:Sialic Acid Binding Ig-like Lectin 2; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; C024275:pokeweed antiviral protein