Biopanning

To widen the search for new treatments, it would be highly beneficial to be able to generate new drugs that act preferentially on diseased cells whilst sparing healthy tissue. It would be ideal if multiple drugs such as these could be isolated simultaneously, without prior knowledge of their targets. At BioInvent we can do just this.

We have developed a differential screening method that enables us to isolate antibodies which recognise one cell type over another from our fully-human recombinant antibody library, n-CoDeR^®. This method involves running positive and negative selections for antibodies using populations of the two cell types. When combined with high throughput functional screening, the most therapeutically active antibodies can be identified. We have called this approach Biopanning. Using this approach we have successfully isolated several disease modifying antibodies that bind to different target structures, some of which were not previously known to be disease modifying. Therefore this technique enables combined target and drug discovery.

These studies have the added advantage of enabling the identification of targets that were not previously known to be associated with a given therapy function, for example triggering tumour cell death. The use of intact target cells in the panning process presents further potential advantages compared to other approaches, including identifying target epitopes (protein, carbohydrate, lipid, or conjugate type) based on their actual expression and their true cell-surface configuration. So target proteins that have a higher level of expression in the pathological state without a corresponding increase in mRNA expression, or epitopes that are generated following post-translational modifications or protein-protein interactions are equally likely to be identified through applying this technology.

We have already used the Biopanning approach to identify antibodies that specifically target cancer cells. The studies involved running positive and negative selections using populations of normal cells and cancer cells. These antibodies could be used as "handles" to specifically trigger tumour cell death through antibody-dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity. To identify the most promising drug candidates we ran a further screen to identify which of these antibodies also have apoptosis-inducing properties. A number of antibodies have come out of this screening process, including BI-505, which is now in clinical development for the treatment of blood cancers.