UNUSUALLY EFFICIENT TUMOR-CELL LYSIS BY HUMAN EFFECTORS OF ANTIBODY-DEPENDENT CELLULAR CYTO-TOXICITY MEDIATED BY MONOCLONAL-ANTIBODIES

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (9) , 3712-3718
Abstract
Concentrations ranging between 0.01 and 10 pg/cell of certain monoclonal antibodies (MAb) were shown to constitute 4-h 50% lethal doses for tumor cells mixed with human effectors of antibody-dependent cellular cytotoxicity (ADCC). This efficient and rapid tumor cell [mouse] lysis is achieved at low effector cell levels (effector:target ratios, .ltoreq. 25:1) at which the effectors were nonadherent peripheral blood leukocytes (PBL) enriched by density centrifugation. Comparable MAb-mediated ADCC efficiency has not been reported previously, probably because most MAb (e.g., 10 of 13 tested in this study) are typically inefficient or completely inactive in mediating ADCC, even at 100-fold greater concentrations. By analyzing the ADCC efficiencies of several MAb specific for murine cell surface alloantigens, it was shown that murine IgG2a and IgG3 MAb and a rat IgG2b MAb are very efficient mediators of ADCC. However, ADCC efficiency was bound not to correlate strictly with subclass, since 4 of 6 murine IgG2a MAb tested were completely inactive, even though they all bound the target cells readily. The relative differences in ADCC efficiencies were not accounted for directly by antibody affinity for antigen; 1 MAb was very efficient in ADCC but had demonstrably low antigen affinity, while a 2nd MAb showed no ADCC activity in spite of its high affinity for the same target antigen. These results point to other experimentally testable properties of MAb and of MAb-antigen complexes which may be critical for efficient ADCC reactions. This study underscores an important immunotherapeutic value which certain MAb potentially have for mediating tumor cell lysis: in low concentrations (and without toxic drug modification), some MAb efficiently mediate the lysis of tumors by ADCC, which itself is as effective as other immune lytic processes but which requires no prior immunological education of effector cells.

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