Target identification in Antibody Drug Discovery is the process of identifying the molecular target of an Antibody - usually target cell surface molecules such as receptors or antigens expressed on tumor cells or other host cells. Steps involve identifying druggable targets (defined as the likelihood of being able to modulate a target with a therapeutic). Target identification can be approached by direct biochemical methods, genetic interactions or computational inference. In many cases, however, combinations of approaches may be required to fully characterize on-target and off-target effects and to understand mechanisms of Ab-binding to the target antigen.
But how is a target selected
What are some of the considerations that go into target selection
What happens after a target is identified
The first step after a target has been identified is to validate it. Validation is simply defined as having gathered adequate scientific evidence for the target's disease association and its therapeutic potential. This is achievable through animal model studies, including mouse genetics. Examples listed below:
Typically a monoclonal antibody (mAb) recognizing the mouse ortholog of the intended human protein is obtained as a surrogate Ab to facilitate target validation. Research materials/reagents at this stage typically include surrogate antibodies, transgenic animals and cell lines. Biological experiments also include knockout, transgenic animals or RNAi techniques. Majority of targets meet some but not all criteria and additional validation efforts are often conducted.
The previous section in this series is "Antibody Drug Discovery Overview". To review, click Here.
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1Shih, H. H. in Development of Antibody-Based Therapeutics (ed M.A; Bornstein Tabrizi, G.G.; Klakamp, S.L.) Ch. 2, 9-32 (Springer, 2012).