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Monoclonal Lym-1 antibody-dependent lysis of B-lymphoblastoid tumor targets
by human complement and cytokinine-exposed mononuclear and neutrophilic
polymorphonuclear leukocytes
L Ottonello, P Morone, P Dapino and F Dallegri
First Medical Clinic, Department of Internal Medicine, University of
Genova, Genova, Italy.
Lym-1 is a murine IgG2a monoclonal antibody that recognizes a polymorphic
variant of HLA-DR antigens on malignant B cells, with minimal
cross-reactivity with normal tissues. Because it can be safely administered
in vivo, a detailed knowledge of its ability to recruit and trigger the
antitumor immune effector systems is required to optimize potential
serotherapeutic approaches in B-lymphoma patients. By using Raji cells as a
model of B-lymphoma targets, we found that Lym- 1 activates
complement-mediated lysis efficiently. Moreover, Lym-1 was capable of
triggering the antibody-dependent cellular cytolysis (ADCC) by peripheral
blood mononuclear cells (MNCs). On the contrary, it failed to trigger
neutrophilic polymorphonuclear leukocyte (PMN)- mediated ADCC activity. In
an attempt to enhance Lym-1 ADCC by MNCs and PMNs, nine biologic response
modifiers were tested. MNC-mediated Lym-1 ADCC was significantly stimulated
by interleukin-2 (IL-2) and unaffected by other mediators, including
gamma-interferon (gamma-IFN), tumor necrosis factor a (TNFalpha), and
granulocyte-macrophage colony- stimulating factor (GM-CSF). On the other
hand, PMN-mediated Lym-1 ADCC was induced or significantly augmented by
various cytokines, such as GM- CSF, TNFalpha, and gamma-IFN, and
chemotaxins, such as formyl peptides (FMLP), complement fragment C5a, and
IL-8. Both MNC- and PMN-mediated ADCC was unaffected by granulocyte
colony-stimulating factor (G- CSF) and insulin-like growth factor-1
(IGF-1). Finally, only GM-CSF and TNFalpha augmented the number of PMNs
actually engaged in the binding of Raji target cells. The findings
presented here, in particular those showing stimulatory activity of
biologic response modifiers, may inspire new attempts for developing Lym-1
antibody-based approaches to the therapy of B lymphomas.
Volume 87,
Issue 12,
pp. 5171-5178,
06/15/1996
Copyright © 1996 by The American Society of Hematology

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