Absolute requirement of CD11/CD18 adhesion molecules, FcRII, and the phosphatidylinositol-linked FcRIII for monoclonal antibody-mediated neutrophil antihuman tumor cytotoxicity Journal Article


Authors: Kushner, B. H.; Cheung, N. K. V.
Article Title: Absolute requirement of CD11/CD18 adhesion molecules, FcRII, and the phosphatidylinositol-linked FcRIII for monoclonal antibody-mediated neutrophil antihuman tumor cytotoxicity
Abstract: We have previously shown that 3F8, a murine IgG3 monoclonal antibody (MoAb) specific for the ganglioside GD2, mediates tumor cell kill in vitro and in vivo. We now describe receptor requirements of polymorphonuclear leukocytes (PMN) in 3F8-mediated cytotoxicity (ADCC) of human GD2(+) melanoma and neuroblastoma cell lines. PMN from a child with leukocyte adhesion deficiency (LAD) were devoid of CD11/CD18 adhesion molecules and mounted no detectable ADCC. MoAb to CD11b, CD11c, and CD18 each efficiently blocked ADCC by normal PMN. In contrast, a panel of different MoAbs to CD11a had no significant inhibitory effect on ADCC, a finding consistent with the low-to-absent expres-sion of the CDIIa ligand, intercellular adhesion molecule-1, on the target cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly increased the expression of CD11b, CD11c, and CD18 on normal PMN, decreased the expression of Fc receptors (FcR), and enhanced ADCC by normal but not by LAD PMN. MoAbs to FcRII and FcRIII each efficiently blocked ADCC; anti-FcRI MoAb had no effect. Flow cytometry using anti-FcRII MoAb versus anti-FcRIII MoAb did not show cross competition, suggesting that inhibition of ADCC was not a steric effect resulting from FcRII proximity to FcRIII. PMN deficient in FcRIII (obtained from patients with paroxysmal nocturnal hemoglobinuria) and PMN depleted of FcRIII by treatment with elastase or phosphatidylinositol (PI)-specific phospholipase C produced low ADCC, supporting a role for the PI-linked FcRIII. Thus, optimal ADCC using human PMN, human solid tumor cells, and a clinically active MoAb (conditions that contrast with the heterologous antibodies and nonhuman or nonneoplastic targets used in most models of PMN ADCC) required CD11b, CD11c, FcRII, and the PI-linked FcRIII. Furthermore, in this clinically relevant system, GM-CSF enhancement of antitumor PMN ADCC correlated with increased expression of CD11 /CD18 molecules. © 1992 by The American Society of Hematology.
Keywords: controlled study; human cell; conference paper; neoplasms; antigen expression; granulocyte macrophage colony stimulating factor; antineoplastic activity; monoclonal antibody; antibodies, monoclonal; neutrophil; neuroblastoma cell; tumor cell line; melanoma cell; fc receptor; neutrophils; antigens, cd; immunoglobulin g3; antibody dependent cellular cytotoxicity; granulocyte-macrophage colony-stimulating factor; lymphocyte function associated antigen 1; glycoprotein p 15095; receptors, fc; elastase; phosphatidylinositols; leukocyte adherence; antigens, cd18; phospholipase c; antigens, cd11; antibody-dependent cell cytotoxicity; human; priority journal; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
Journal Title: Blood
Volume: 79
Issue: 6
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 1992-03-15
Start Page: 1484
End Page: 1490
Language: English
PUBMED: 1347707
PROVIDER: scopus
DOI: 10.1182/blood.V79.6.1484.1484
DOI/URL:
Notes: Article -- Export Date: 30 July 2019 -- Source: Scopus
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MSK Authors
  1. Brian Kushner
    271 Kushner
  2. Nai-Kong Cheung
    579 Cheung