RRC ID |
59869
|
著者 |
Hirosaki H, Maeda Y, Shimojima M, Maeda K, Iwata H, Takeyoshi M.
|
タイトル |
Effects of Soluble Tumor Necrosis Factor (TNF) on Antibody-Dependent Cellular Cytotoxicity of Therapeutic anti-TNF-α Antibody.
|
ジャーナル |
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.
|
巻・号 |
48(5)
|
ページ |
441-450
|
公開日 |
2019-7-1
|
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
|
引用数 |
2
|
リソース情報 |
ヒト・動物細胞 |
CHO-K1 |