Monoclonal antibodies (mAbs) have emerged as powerful approaches for treating cancer. The induction of effector functions through the Fc region of the antibody is considered to be significant for antibody therapeutics developed to eliminate tumor cells. Since antibody-dependent cell-mediated phagocytosis (ADCP) is an important mechanism of action (MOA) of therapeutic antibodies, Creative Biolabs now provides high-quality ADCP reporter assays to assist our clients in new innovator or biosimilar therapeutic antibody development.
Performing ADCP using primary macrophages derived from healthy donors as effector cells is regarded as a time-consuming and challenging method where target cell phagocytosis is the end-point. ADCP reporter assay with luminescence readout is an alternative approach, in which the ADCP pathway activation via the H131 variant of the FcγRIIa (CD32a) receptor is measured. FcγRIIa is a major FcγR in ADCP by macrophages. The ADCP reporter assay is analogous to primary ADCP assays regarding the signaling pathway but avoids using primary macrophages.
The ADCP reporter assay eliminates variability related to traditional ADCP bioassays with equal sensitivity and much better signal to noise ratio. The availability of FcγRIIa effector cells within a reporter-based ADCP assay makes it possible to perform fast, accurate, precise, reproducible and cost-saving testing with an improved reflection of in vivo bioactivity during early-stage biocomparability as well as for stability and lot release testing.
Fig.1 FcγR-mediated effector pathways during viral infection. (Eyre, 2015)
For ADCP reporter assay, we replace primary cells with an engineered Jurkat cell line stably expressing human FcγRIIa (CD32a) H-131 and NFAT-induced luciferase as effector cells. After engaging with the Fc region of a relevant antibody that binds to a target diseased cell, ADCP bioassay effector cells expressing FcγRIIa-H131 with transducing intracellular signals leading to NFAT-RE-mediated luciferase activity which can be easily measured and quantified.
Scientists at Creative Biolabs have deep insight and extensive experience in the functional requirements of antibodies and are industry leaders in the analysis and characterization of the effector function of therapeutic antibodies. Equipped with proprietary technology and cell line development capabilities, we are able to develop custom ADCP assays across a variety of different formats to support your study on antibody drug development at all stages of development.
Now, we provide two distinct well-established assay formats for ADCP evaluating:
A combination of both approaches permits ADCP bioactivity to be performed during the whole life cycle of a therapeutic antibody.
In addition to ADCP assays, Creative Biolabs also offers the following services regarding Fc-mediated Effector Functional Assays:
If you have any special needs in primary ADCP assays or be interested in learning more about Creative Biolabs’ ADCP assay services, please contact us for more information.
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