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Anti-CD19 inhibits the growth of human B-cell tumor lines in vitro and of
Daudi cells in SCID mice by inducing cell cycle arrest
MA Ghetie, LJ Picker, JA Richardson, K Tucker, JW Uhr and ES Vitetta
Department of Microbiology, University of Texas Southwestern Medical
Center, Dallas 75235-8576.
In this report, we extend our previous findings that IgG or F(ab')2
fragments of HD37 anti-CD19 antibody (Ab) in combination with the
immunotoxin (IT), RFB4-anti-CD22-deglycosylated ricin A chain (dgA) (but
neither reagent alone), prolonged the survival of SCID mice with
disseminated human Daudi lymphoma (SCID/Daudi mice) to 1 year at which time
they still remained tumor-free. We explored the mechanisms by which the
HD37 Ab exerts antitumor activity in vivo by studying its activity in
vitro. We found that it has antiproliferative activity (IC50 = 5.2 - 9.8 x
10(-7) mol/L) on three CD19+ Burkitt's lymphoma cell lines (Daudi, Raji,
and Namalwa) but not on a weakly CD19-positive (CD19lo) pre-B cell tumor
(Nalm-6). The inhibitory effect was manifested by cell cycle arrest, but
not apoptosis. Results using three additional anti-CD19 Abs, suggest that
the affinity of the antibody and possibly the epitope which it recognizes
may effect its capacity to transmit a signal that induces cell cycle
arrest. Hence, therapeutically useful Abs may exert anti-tumor activity by
a variety of mechanisms, each of which should be evaluated before
undertaking clinical trials in humans.
Volume 83,
Issue 5,
pp. 1329-1336,
03/01/1994
Copyright © 1994 by The American Society of Hematology
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