RRC ID 59869
Author Hirosaki H, Maeda Y, Shimojima M, Maeda K, Iwata H, Takeyoshi M.
Title Effects of Soluble Tumor Necrosis Factor (TNF) on Antibody-Dependent Cellular Cytotoxicity of Therapeutic anti-TNF-α Antibody.
Journal Immunol Invest
Abstract Anti-TNF antibodies are major therapeutics for rheumatoid arthritis and have been approved for marketing in many countries. Antibody-dependent cellular cytotoxicity (ADCC) is considered to be a potential mechanism of action of anti-TNF antibodies, since some anti-TNF antibodies have been confirmed to induce cytotoxic effects on TNF-producing cells via ADCC and complement-dependent cytotoxicity (CDC) in in vitro experiments. In this study, we established a new stable effector cell line expressing human FcγRIIIa, CD16:KHYG-1, and compared the performance of this cell line with that of peripheral blood mononuclear cells (PBMCs) in ADCC assays against CHO-derived target cells expressing protease-sensitive pro-TNF. Although an inhibitory effect of soluble TNF released from pro-TNF expressing cells on ADCC activity was seen, clear dose-responsive ADCC activities were observed even in the presence or absence of TNF-α converting enzyme (TACE) inhibitor. However, significant differences in the ADCC activities in the presence or absence of TACE inhibitor were only noted when CD16:KHYG-1 cells were used as the effector cells. Our findings indicate that soluble TNF may influence ADCC activity of anti-TNF antibody. Moreover, the fact that the influence was able to be detected only in the case using stable effector cell also suggests that the stable effector cell established this time enable highly accurate ADCC measurement.
Volume 48(5)
Pages 441-450
Published 2019-7
DOI 10.1080/08820139.2018.1549067
PMID 30569777
MeSH ADAM17 Protein / metabolism Animals Antibody-Dependent Cell Cytotoxicity Arthritis, Rheumatoid / drug therapy* CHO Cells Cell Line Cricetulus Dipeptides / pharmacology Humans Hydroxamic Acids / pharmacology Infliximab / pharmacology Infliximab / therapeutic use* Killer Cells, Natural / immunology* Killer Cells, Natural / pathology Leukocytes, Mononuclear / immunology* Receptors, IgG / genetics Receptors, IgG / metabolism Transgenes / genetics Tumor Necrosis Factor-alpha / immunology Tumor Necrosis Factor-alpha / metabolism*
IF 2.687
Times Cited 2
Human and Animal Cells CHO-K1