In tumor microenvironment with human native immune system, once the tumor-specific targets are recognized by a particular antibody drug, the Fc part of the antibody would bind to the FcγR of native immune cells (such as NK cells and macrophages) and activate them, thereby eliciting effector functions to kill or phagocytose the target cancer cells. The Fc part of the antibody drug may also bind to the complement protein C1q in human serum, activating the complement system and eventually forming membrane attack complex which may act on the membrane of the target cancer cells and lyse them (See the graph below). We may utilize the MoA (Mechanism of Action) of these native immune cells to assess the functionalities of the antibody drugs in vitro.
Figure: Antibody-mediated immune cell functional assays, including Antibody-Dependent Cellular Cytotoxicity (ADCC), Complement-Dependent Cytotoxicity (CDC), and Antibody-Dependent Cellular Phagocytosis (ADCP)
ADCC, CDC and ADCP assays are relatively complex experiments, and many factors play roles to determine the success of the assay, including:
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There are three formats of ADCC assays at in vitro bioassay platform:
ADCC Service Key Features:
*CD20, Her2, CD38, EGFR, mTNFα, B7H3, Claudin 6, and Claudin 18.2 etc.
CDC assay service key features:
*CD20, CD38, mTNFα, B7H3, Claudin 6, and Claudin 18.2 etc.
There are three formats of ADCP assays at in vitro bioassay platform:
ADCP Service Key Features:
*CD20, CD38, CD47/Sirpα, and Claudin 18.2 etc.
Brief information on detection method of ADCP assay:
Two distinct fluorescence dye are used to label target cell and effector cell respectively. Macrophages with target cell engulfed will show double positive fluorescence signal (See Q2 in the figure below).
“The quality of every bioactive component in ADCC, CDC and ADCP assays is critical to ensure the success of these experiments! QC is the key! ”
Dr Zhuo Fang
Senior Scientist for in vitro bioassay service platform in GenScript ProBio