The activity of many antibody-based therapeutics is mediated in part by their ability to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and thereby enhancing the body’s own immune response towards dysfunctional cells. Furthermore, extensive requirements for analytical characterization are now needed to show comparability between innovator drug and biosimilar. By analyzing the ADCC activity induced by different drugs or drug candidates, a measure of both drug potency and unwanted side effects can be provided as well as establishing the suggested ADCC mechanism of the drug candidate.
The iLite ADCC product line is a valuable tool for the whole drug development process, measuring the ability of a drug to induce ADCC activity in a straight forward, sensitive and reproducible manner.
The iLite ADCC product line includes an engineer effector cells expressing the FC receptor, a specific positive target cell as well as a negative control cell line for each specific target. These targets cells allow screening for specific as wells as unspecific activation of ADCC, giving added value to each experiment.
As the majority of the iLite cell lines, the iLite ADCC Effector Cells also have a secondary luciferase readout, from a luciferase expressed under the control of a constitutive promotor. This enables normalization of each individual readout according to cell number and thereby accounts for any potential matrix effects.
The interaction between the reporter gene effector cell and the target cell, generated by the crosslinking of the two cells via a specific drug antibody. The resulting luminescence originates exclusively from this crosslinking and the signaling from the CD16 receptor to the Firefly Luciferase promoter. The strength of the luminescence correlates to the drugs ability to induce ADCC.
When the target cell has been depleted for the specific surface target molecule, the crosslinking between the effector and the target cell cannot be established and hence no luminescence from Firefly Luciferase is generated. However, luminescence from the normalization gene, which is expressed under a constitutive promotor, is still present.