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D Cemerlic, B Dadey, T Han and L Vaickus
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263.
The feasibility of combining the Lym-1 monoclonal antibody (MoAb) with
interferon-gamma (IFN-gamma) in the treatment of chronic lymphocytic
leukemia (CLL) was evaluated. We used an in vitro tumor lysis model that
incorporated fresh CLL cells from 21 different patients as targets for two
distinct normal human leukocyte effector subsets, neutrophils, and
peripheral blood mononuclear cells (PBMCs). Lym-1 antigen (Lym-1- Ag)
expression varied greatly and did not correlate with the expression of
other CLL-associated antigens such as CD5, CD19, or HLA-DR. CLL cells were
not lysed by neutrophils alone or with IFN-gamma in the absence of Lym-1.
Neutrophil Lym-1-dependent cytotoxicity (ADCC) in the absence of IFN-gamma
was weak and inconsistent. IFN-gamma exposure induced MoAb-dependent lysis
of 80% of 21 CLL targets and resulted in an eightfold augmentation of
neutrophil ADCC against the remainder. Cytotoxicity correlated directly and
positively with Lym-1-Ag expression. Confirmation of the need for
interaction between neutrophil IgG Fc receptors (Fc gamma Rs) and the Fc
portion of the Lym-1 MoAb was obtained by demonstrating that purified
Staphylococcus aureus Protein A (SpA) inhibited ADCC. IFN-gamma exposure
caused no consistent alternations in Lym-1-Ag expression on CLL cells so
that target antigen upregulation was unlikely to account for augmentation
of neutrophil ADCC. PBMCs alone, exposed to interkeukin-2 (IL-2) or
IFN-gamma, or with Lym-1 in the presence or absence of IL-2 or IFN-gamma
were unable to lyse CLL targets. PBMCs were able to kill Raji Burkitt
lymphoma cells in conjunction with Lym-1, so their ability to interact with
Lym- 1-coated targets and their lytic functions appeared intact. These
results emphasize the importance of examining fresh tumor cells with
different leukocyte effector subsets before designing a clinical trial that
combines a therapeutic MoAb with a cytokine.
This article has been cited by other articles:
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| Copyright © 1991 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
