Building small-molecule-controlled biologics...

Monoclonal antibody (MAb) therapies are a new frontier of pharmaceuticals used for treating a variety of illnesses such cancer. However, the administration of MAbs may be associated with an overactive immune response that cause extremely dangerous side effects. To help solve this problem we created an antibody kill switch in which a small molecule can quickly turn the antibody “off” in the body and mitigate these side effects. Using computer protein modeling, we engineered an antibody with two compartments, the first consists of the variable antibody domains while the second is our kill switch. This kill switch region is AraC, a bacterial transcription factor that forms a homodimer that dramatically changes its dimer orientation when bound to the small molecule arabinose. In our design, when arabinose binds the AraC compartment, it pulls apart the homodimer, rendering our antibody nonfunctional. This concept could create a new generation of safer monoclonal antibodies.

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