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Killing of autologous B-lineage malignancy using CD3 x CD19 bispecific
monoclonal antibody in end stage leukemia and lymphoma
IA Haagen, AJ Geerars, WB de Lau, MR Clark, RJ van de Griend, BJ Bast and BC de Gast
Department of Immunology, University Hospital Utrecht, The Netherlands.
To develop an effective tumor immunotherapy for B-lineage non-Hodgkin's
lymphoma (NHL) and acute lymphoblastic leukemia (ALL), a bispecific
monoclonal antibody (BsAb) has been generated with the first specificity
for the CD3 epsilon-chain and the second for the CD19 antigen. Peripheral
blood mononuclear cells (PBMCs) isolated from patients with NHL or ALL
during remission or relapse rapidly proliferated (up to 179-fold increase)
on in vitro activation combining phytohemagglutinin or CD3 monoclonal
antibody with interleukin-2. After 3 weeks of stimulation, more than 90% of
the PBMCs was CD3+ and CD8+, even when cultures were started with only 5%
CD3+ cells. Cytotoxic activity against autologous malignant B cells was
markedly enhanced (from 5% baseline to 70% lysis) by the addition of the
CD3 x CD19 BsAb in all samples tested. Immunophenotypic examination of a
series of tumor target cells showed that all samples examined showed CD54
(intercellular adhesion molecule-1) and HLA class I, but showed no B7
expression. CD11a (lymphocyte function-associated antigen-1) expression was
heterogeneous. Various types of experiments showed that efficient CD3 x
CD19 BsAb-mediated cytolytic capacity was not dependent on expression of
either of these surface proteins. This contrasts with normal major
histocompatibility complex-restricted antigen-specific cytotoxicity and may
be essential for effective in vivo application of this BsAb.
Volume 84,
Issue 2,
pp. 556-563,
07/15/1994
Copyright © 1994 by The American Society of Hematology
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