Establishment of a cell model for screening antibody drugs against rheumatoid arthritis with ADCC and CDC

Area of Science:

• Immunology
• Pharmacology
• Biotechnology

Background:

• Tumor necrosis factor alpha (TNFα) is central to rheumatoid arthritis (RA) pathogenesis.
• Anti-TNFα agents are effective RA treatments, but their potencies vary due to mechanisms beyond neutralization, such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).
• Differentiating candidate anti-TNFα reagents requires robust assays evaluating these cytotoxic mechanisms.

Purpose of the Study:

• To establish a stable cell model expressing transmembrane TNFα for in vitro ADCC and CDC assays.
• To provide a reliable protocol for screening macromolecular antibody drugs targeting TNFα.
• To enable a deeper understanding of anti-TNFα agent potency beyond simple neutralization.

Main Methods:

• A stable cell subline expressing transmembrane TNFα was created using conventional transfection.
• Transmembrane TNFα expression was confirmed via flow cytometry.
• The cell model's performance in ADCC and CDC assays was evaluated using human peripheral blood mononuclear cells and Adalimumab as the test agent.

Main Results:

• The established cell subline exhibited high surface expression of transmembrane TNFα.
• Adalimumab demonstrated both ADCC and CDC effects on the engineered cell model.
• The cell model proved effective for evaluating cytotoxic mechanisms of anti-TNFα agents.

Conclusions:

• The developed stable cell line is suitable for ADCC and CDC assays in antibody drug screening.
• This model offers a valuable tool for assessing the potency of candidate antibody drugs targeting TNFα.
• The findings contribute to a more comprehensive evaluation of anti-TNFα therapies in drug development.