Post #713: Another promising treatment: monoclonal antibodies

Posted on June 11, 2020

Convalescent plasma is a well-established technique for treating diseases that have no other type of treatment, such as Ebola.  You take blood from individuals who have recovered from a disease, separate out the antibodies that they have developed that fight the pathogen in question, and inject those antibodies into someone else.  Those antibodies then provide “passive immunity” to the person who was injected — they allow that person to fight to pathogen.

This technique has been in use for more than a century, for a wide range of diseases.  Case reports from China and elsewhere suggested that it has some significant benefit in treating COVID-19.  (A fairly exhaustive literature review can be found on this University of Michigan web page. )

Providing antibodies to an infected individual is helpful, but it’s not a silver bullet.  Although there were good early case reports, at least one clinical trial found only modest (and not statistically significant) improvement among critically ill COVID-19 patients.  But that had limitations, including small sample size and a focus on the critically ill (for whom almost nothing appears to work well, including anti-viral drugs).  The modest clinical improvement for the critically ill COVID-19 population appears similar to convalescent plasma results for the earlier MERS coronavirus epidemic (per this reference).  And, administration of convalescent plasma at earlier stages of disease appears to have better results (per this commentary).

Regardless of effectiveness, a shortcoming of convalescent plasma is availability.  Recovered donors with adequately high antibody levels can donate enough blood to treat a handful of cases.  And the equipment that separates out the antibodies appears to be relatively uncommon.

Thus, whatever the level of benefit, this treatment is limited by supply.  (Which is, I think, why it has largely been reserved for critically ill patients, so far.)  There simply does not appear to be a way to extract these naturally-occurring antibodies in large quantities.

So, why not just manufacture the antibodies instead?  And that’s precisely what several drug companies are now attempting to do, using monoclonal antibody techniques.  Under this approach, scientists develop cells that produce an antibody for some specific substance, culture (grow) those cells, then extract the antibody.

Monoclonal antibodies are now a mainstay of treatment for both autoimmune disease and cancer.  Any drug (biological) whose generic name ends in “-mab” is a monoclonal antibody.   Hence, Remicade (infliximab), Humira (adilumimab), Avastin (bevacizumab), among others.  Currently, it looks like 6 of the top 10 drugs sold in the US, by dollar volume, are -mabs.   The list of commercially-available -mabs includes hundreds of substances (per Wikipedia).

This is almost a plug-and-play technology at this point.  Several different systems are commercially available for developing -mabs to produce specific antibodies of interest.  These are common, but they are still high-end science, involving techniques that would have been unthinkable 30 years ago.  For example, one of the oldest and most successful -mabs — Remicade — is actually a mouse-human hybrid.

And so, that machinery is now being focused on COVID-19.  This is now at the clinical trials phase for one of them.  My only point being that this is a completely routine and feasible (if expensive) technology.  There’s no question that they can produce these COVID-19-specific monoclonal antibodies, in large quantities.  At this point, their effectiveness is not clear, particularly for the most severely ill patients.  But these should, at the minimum, add another set of therapies to the list of treatments for COVID-19.