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 10-8M, 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.