Complement activation

Simultaneous study of all complement responses - in one assay.

Get the complete picture of your drug’s interaction with the complement system

Immuneed’s platform based on fresh, circulating human blood is unique in having an intact complement system. The complement system, which comprises around 40 small blood proteins synthesized by the liver, can cause or contribute to reactions that may occur during the infusion of a biological drug. To know your drug’s complete safety profile before entering a clinical trial, an assessment of complement activation is vital.
Complement activation starts a cascading immune response that stimulates phagocyte action, inflammation and membrane attack complex, which can play a role in multiple types of hypersensitivity reactions. These include reactions based on complement-dependent cytotoxicity (CDC), which can be prevented through antibody modification. But they also include reactions based on antibody-dependent cell-mediated cytotoxicity (ADCC), which is frequently overlooked. The latter can occur via the alternative pathway, which remains active even when the classical pathway has been blocked.

A study of complement activation levels

Shown above is a direct comparison of Immuneed’s platform with two plate-based assays where either PBMCs with coated antibodies or whole blood with soluble antibodies were used for cytokine release assessment. It involves antibodies associated with a low risk of causing CRS, namely anti-integrin alpha 4 (1 µg/ml) and anti-EGFR antibody (200 µg/ml), as well antibodies associated with a high risk of CRS, namely anti-CD52 antibody (3 µg/ml) and anti-CD28 (aCD28). The level of cytokines was compared to vehicle and zero (blood directly after the acquisition). In the Immuneed assay, cytokine release was measured at a time point of 4 hours, while the plate-based assays required a 24-hour incubation time before readouts could be taken.

Choose Immuneed to:

Your drug is infused into fresh human blood in circulation.
Read-outs are taken to perfectly mimic the clinical situation of infusion reactions.
The multiplexing platform from MesoScale Discovery (MSD) is used for analyzing the samples.
The MSD platform supplies over 100 validated immunoassays that deliver reproducible and reliable results.

Testing methods and capabilities:

Simultaneous evaluation of CDC and ADCC
Complement activation: C3a, C5a and SC5b-9
Complete blood count: hematology parameters

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5 step guide

Five-step guide to improving preclinical testing from a complement perspective. When evaluating drug function and safety, don’t overlook – or underestimate – the complement system.