B-cell restricted saporin immunotoxins: activity against B-cell lines and
chronic lymphocytic leukemia cells
M Bregni, S Siena, A Formosa, DA Lappi, D Martineau, F Malavasi, B Dorken, G Bonadonna and AM Gianni
Division of Medical Oncology, Istituto Nazionale Tumori, Milano, Italy.
B cell-restricted immunotoxins were constructed by conjugating anti-B
monoclonal antibodies to saporin, the major ribosome inactivating protein
from the seeds of the plant Saponaria officinalis. HD37-SAP is directed
against CD19, the broadest B cell-specific determinant. HD39- SAP and
HD6-SAP recognize two different epitopes on the CD22 molecule, an antigen
present on the cell surface of B cells at late stages of differentiation.
All three immunotoxins inhibited DNA synthesis and protein synthesis in
target B lymphoma cells with a dose-related effect, in short incubation
times and in the absence of potentiators. A clonogenic assay demonstrated
that all immunotoxins could eliminate more than two logs of clonogenic
malignant B cells with a two-hour incubation at concentrations not toxic to
cells not bearing target antigens. The immunotoxin activity was evaluated
by DNA synthesis inhibition in fresh B-chronic lymphocytic leukemia cells
(B-CLL) stimulated to proliferate by incubation with an antibody specific
for the receptor of C3b complement component (CR1) plus B cell growth
factor. B-CLL cell DNA synthesis was actively inhibited by treatment at low
immunotoxin concentration without need of potentiators. Immunotoxins
exerted their effect also in whole blood of CLL patients under conditions
achievable in vivo. We conclude that B cell-restricted immunotoxins
HD37-SAP, HD39-SAP, and HD6-SAP are good candidates for in vivo therapy of
B-cell malignancies.
Volume 73,
Issue 3,
pp. 753-762,
02/15/1989
Copyright © 1989 by The American Society of Hematology
