A recently published study investigated the use of synthetic antibodies as enzyme inhibitors for therapeutic benefits, particularly matrix metalloproteinases (MMPs) involved in the pathogenesis of cancer.
Enzymes are proteins that catalyze chemical reactions and are necessary for most physiological processes in the body. Matrix metalloproteinases (MMPs) are a category of protease enzymes that are also involved in many pathological, in addition to physiological, processes such as cancer, hypertension and neurological pain. As a result, certain MMPs have been identified as promising drug targets for therapeutic intervention. Small molecules are typically used to inhibit MMPs, yet often result in off-target side effects because they are nonspecific and can inhibit multiple enzymes, even those involved in healthy processes. An alternative to small molecules are antibodies. Antibodies are more recently being investigated for their ability to inhibit MMPs because of their high specificity and low toxicity. The limitation of human antibodies, however, lies in their shape, which is incompatible with that of most MMPs, rendering them unable to bind and inhibit. On the contrary, camel antibodies have a more desirable shape that enables them to inhibit enzymatic reactions.
In their study, Nam and the study team in the Department of Chemical and Environmental Engineering at the University of California sought to synthesize human antibodies with the ability to inhibit enzymatic reactions. They analyzed the structure of over 900 camel antibodies and 90,000 human antibodies from various databases, and developed a library of human antibodies that carry a partial structure of camel antibodies. They then investigated the use of synthetic antibodies as enzyme inhibitors for therapeutic purposes. According to their findings, published in Proceedings of the National Academy of Sciences, the researchers identified twenty antibodies in their library that inhibited MMP-14, an enzyme shown to be involved in the development of cancer. In particular, fourteen of the twenty antibodies potently and specifically inhibited MMP-14, without exhibiting off-target effects. While this is promising, further testing needs to be done to determine if these antibodies can affect cancer progression in the human body.
This study investigated the use of synthetic antibodies as enzyme inhibitors for therapeutic benefits, and provided a rich pool of lead candidates for further testing of their therapeutic efficacy. The pipeline established by these researchers can now be applied in the future for the development of synthetic antibodies with inhibitory or other therapeutic purposes.
Written By: Danielle Vitali, BSc