ADCC / CDC

Simultaneous study of ADCC and CDC

Customer Promise

BALANCE

Strike the right balance between the safety and efficacy of your antibody.

EFFICIENCY

ID.Flow allows ADCC & CDC to be studied simultaneously, which is unique in preclinical testing.

FLEXIBILITY

Tailored study design and flexible scientific reports.

ADCC & CDC

Strike the right balance between safety and efficacy

The need to thoroughly understand and optimize the risk-benefit ratio of engineered antibodies remains a challenge for many companies.  Changing the Fc region of an antibody to enhance complement-dependent cytotoxicity (CDC) may make it more immunogenic as a result of its physicochemical properties or sequence. The same applies to antibody-drug conjugates (ADCs). Multiple binding sites may make the antibody more effective, but it may also make it more prone to form immune complexes.  An antibody designed to enhance Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) may stimulate excessive cytokine release from several effector cells or lead to a changed degradation pattern.

We offer tailored preclinical testing of ADCC and CDC in fresh circulating human whole blood with an active complement and cascade system. This is unique for the Immuneed platform (ID.Flow). Schedule a meeting with us to discuss your project and how we can tailor the study to address your specific needs. Drop us a line here.

CDC & ADCC assay

Strike the balance between safety and efficacy
Characterize your drug in a physiologically relevant environment.
Get a thorough understanding of cell binding and activation in blood.
Get multiple readouts from the same sample, at different time points.

Readouts

CDC complement activation: C3a and C5a.
ADCC by detection of NK cell activation: surface CD69 and CD107a, or intracellular IFNg/TNFa.
Target cell viability: flow cytometry/hematology parameters.
CDC/ADCC functional assessment: performed by blocking ADCC (CD16 block) and CDC (C1q, C3, C5 block) and looking at the effects of the parameters described above.

Mode of action of immune inhibitor drugs

Many drugs inhibit the immune system. This can be studied by introducing a broad stimulus (e.g. a low dose of LPS) or a target-specific stimulus (e.g. an agonistic T cell-specific antibody) and observing whether the drug inhibits the immune activation of that stimulus. A variety of readouts can be included to characterize the immune profile for the inhibitory response such as cell activation, cytokine release, and complement activation.

Fc binding assay for therapeutic monoclonal antibodies

Antibodies produce a therapeutic effect by binding target cells, which has a net effect that may be antagonistic, agonistic, blocking, or cell-depleting. When a target cell is bound by a monoclonal antibody, two mechanisms can lead to the cell’s death: ADCC or CDC. The responsible killing mechanism can thus be identified for antibodies known to result in target cell death, simply by specifically blocking one mechanism or the other. The activation profile of the effector cells can be combined with viability monitoring of the target cells.

ADCC and CDC mechanism

Antibodies can induce two major mechanisms that lead to target cell death: ADCC or CDC. ADCC is induced when the target-bound antibody is recognized by FcγRs on effector cells that cause cell lysis of the target cell (left). CDC is induced when the target-bound antibody is recognized by C1q, causing a cascade of events that result in the release of soluble C3a and C5a and the formation of the membrane attack complex (MAC) that lyses the target cell (right).

Contact

Have a project or a question? We'd be happy to hear from you.

5 step guide

Your five-step guide to improving preclinical testing from a complement perspective. Learn how to predict complement system behavior in the best way.