Which Cell Line Models ADCC Most Reliably?

• • For reproducibility and screening: an FcγRIIIa reporter line (NFAT-luciferase) — quantitative, no donor variability, high throughput.
• • For physiological relevance: primary NK cells, ideally from multiple donors, with the FcγRIIIa genotype reported.
• • For a middle ground: an NK line such as NK-92 derivatives, which are consistent but carry a fixed receptor repertoire.

None of them measures killing if it is a reporter assay; none of them is reproducible across donors if it is primary cells. State which property you need.

Whether you need killing or engagement. Reporter assays measure receptor activation. If the claim is "this antibody mediates ADCC", engagement is a proxy; if the claim is "this antibody kills target cells", you need a killing readout.

Whether donors are acceptable as a variable. Primary NK cells introduce donor variability that is itself informative — but it demands replication at the donor level, which most screening designs cannot afford.

Whether the target antigen density is physiological. A reporter assay on a high-antigen target line will look excellent regardless of effector choice; the effector comparison only becomes meaningful when antigen density is realistic.

A two-layer design covers both needs:

1. Screen with the reporter line — rank antibodies or CAR constructs by Fc engagement, with antigen-density controls.
2. Confirm the top candidates with primary NK cells from at least two donors, reporting FcγRIIIa genotype, at multiple effector-to-target ratios.

This sequence is cheap where it can be and physiological where it matters.

EDITGENE supplies FcγRIIIa reporter lines with documented receptor variant, NK-92 derivatives, and antigen-density target panels — plus assay support for primary NK confirmation.

Tell us the target and the mechanism. Contact EDITGENE to request a project consultation or quote.

Effector performance depends on receptor genotype, antigen density, ratio, and assay duration; results across effector systems are not directly comparable.

Reporter assays measure activation, not lysis; killing claims require a killing readout.

• • Clynes RA, et al. Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nature Medicine. 2000;6:443–446.
• • Majzner RG, et al. Tuning the antigen density requirement for CAR T-cell activity. Cancer Discovery. 2020;10:702–723.
• • Liu X, et al. Fc engineering for developing therapeutic antibodies. Antibody Therapeutics. 2020;3:1–10.