Monday, December 3, 2012

New Options for ADCC Assays

The success of biologic therapeutics has begun to reshape today’s pharmaceutical market.  The first and most successful of these antibody therapies, Rituximab (Rituxan®; Roche/Genentech), showed worldwide sales in 2009 of $5.6 billion (GEN News Highlights, 2011).  This, among others including Trastuzumab (Herceptin®; F Hoffman-La Roche), have shown great promise for treatment of patients with leukemia, lymphomas, breast, and other cancer types due to their specificity and reduced side effects (Zhou, 2007).  One of the mechanisms which play a central role in the response to clinical antibody therapy is antibody-dependent cell-mediated cytotoxicity (ADCC) (Wang, 2008).  This involves the response of natural killer (NK) cells to bind to specific antibody-coated target cells, such as CD20 and HER2 expressing cells, to promote the death of the target cell. 

With many of the existing patents covering these treatments set to expire in the next few years, the development of biologic therapeutics similar to the original drug (biosimilars) has become increasingly important.  As a direct result, assays that can assess the ability of a biosimilar to act in a manner similar to the original biologic have also seen increased interest. The current “gold standard” ADCC assay incorporates 51Cr.  The procedure involves labeling and incubating target cells with the radioligand, assessment of the labeling procedure, and finally performance of the actual assay. Not only is this time consuming, but involves the use and eventual costly disposal of radioactive material. Newer ADCC assays, however, have recently been developed. They have incorporated luminescent, time-resolved fluorescence (TRF), or homogeneous time-resolved fluorescence (HTRF) technologies in substitution for the previously used radioligand.  These assay chemistries have proven to be easier to use and more amenable to automation, while still delivering accurate results.

Recently BioTek presented a webinar discussing these new chemistries, and how they can be automated in 96- or 384-well format. We invite you to view the information presented and learn how the combination of assay and automation can provide robust, hands-free, higher throughput processing for the development of new antibody therapeutics.

By Brad Larson, Principal Scientist

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