Tocilizumab – a new Covid-19 drug obtained through genetics

Last week, almost buried by the latest positive announcements on Covid-19 vaccines, was the good news of a successful drug trial.  Tocilizumab, a drug used for the treatment of severe arthritis, has been shown to more than halve the death rate in hospitalised patients with severe Covid-19 pneumonia.

In severe Covid-19 infections, over-activity of the patient’s immune system presents a danger to their survival, so doctors have been looking for ways to damp down this excessive response. The anti-inflammatory steroid, dexamethasone, was the first drug shown to have positive effects in this way. Now tocilizumab, which has previously been used to reduce immune over-activity in rheumatoid arthritis has been proven to benefit patients with severe Covid-19.   

Tocilizumab works in a completely different way from dexamethasone.  It specifically targets and blocks a protein on a major activation pathway which normally acts to trigger immune reactions.  By blocking this particular protein, immune activation is reduced. So what does this have to do with genetics?

Well firstly, like many proteins in the immune system, the targeted protein could only be identified by first finding its gene.  Secondly, once this gene hunting was successful, genetic engineering within research laboratories was needed to study the properties of this protein, and to raise an antibody which would recognise it specifically.   

Finally, this antibody was initially generated in a laboratory mouse, so it is a mouse-derived antibody.  As a foreign antibody it will not work well once administered into patients.  The patient’s immune system will start to neutralise and remove it. To avoid this, more genetic engineering is needed to snip out the small elements of the antibody which actually bind to the target and graft them into a human antibody backbone.  Such an antibody is now mostly of human origin and is therefore referred to as a humanized antibody.

Increasingly some our new important and most powerful medicines are humanized antibodies, for use in the treatment of serious diseases including rheumatoid arthritis and cancer.

In the case of tocilizumab, it still needs licence approval for use in severe Covid-19 infection, but since there is much clinical experience of its use in rheumatoid arthritis, this should be a straight-forward process. We can therefore be confident that we now have a new brick in the wall of our defences against the coronavirus.

©CC Rider

23rd Nov 2020

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