Antibody-dependent, cell-mediated cytotoxicity by an anti-class II murine monoclonal antibody: effects of recombinant interleukin 2 on human effector cell lysis of human B-cell tumors.
Lym-1 is an IgG2a murine monoclonal antibody that reacts with variant Class II molecules expressed on B-cell malignancies. Lym-1 was shown to mediate antibody-dependent cellular cytotoxicity (ADCC) of human effector cells against a variety of malignant B-cell lines. Tumor cell lysis was Lym-1 specific because (a) the reaction was dose dependent with significant ADCC detectable at Lym-1 concentrations as low as 1 microgram/ml; (b) tumor targets not expressing the Lym-1 antigen were unaffected; (c) an isotype-matched irrelevant monoclonal antibody and an IgG1 anti-Class II monoclonal antibody failed to mediate ADCC; and (d) addition of Protein A (which binds avidly to Lym-1) blocked ADCC by 90 to 100%. Peripheral blood mononuclear cells obtained from normal donors as well as from cancer patients were able to interact with Lym-1 to elicit ADCC. Recombinant interleukin 2 (rIL-2) enhanced non-antibody-mediated tumor lysis and Lym-1 ADCC with an optimal concentration of 100 units/ml. Pulse treatment of normal peripheral blood mononuclear cells with rIL-2 was able to augment Lym-1 ADCC but was less effective than having the rIL-2 present through the assay. Peripheral blood mononuclear cells obtained from patients being treated with high doses of rIL-2 administered by continuous i.v. infusion demonstrated Lym-1 ADCC levels which were higher than normal individuals and which were further augmented by in vitro incubation with rIL-2.
Biddle
W C
WC
Division of Clinical Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263.
Pancook
J
J
Goldrosen
M
M
Han
T
T
Foon
K A
KA
Vaickus
L
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D000951:Antigens, Neoplasm / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D006681:HLA-D Antigens / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007945:Leukemia, Lymphoid / Q000276:immunology*; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology*; D051379:Mice; D011961:Receptors, Fc
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006681:HLA-D Antigens; D007376:Interleukin-2; D011961:Receptors, Fc