Currently there is no evidence-based targeted treatment for COVID-19,
but the landscape for potential treatments is growing.
One particular drug class, monoclonal antibodies,
is generating some cautious optimism among researchers.
Many of us, I think, looking at the landscape would say, "If there's a hope for something
with a big effect size, I think there's evidence, based on other circumstances,
but nothing you can be sure of, is monoclonals derived
from people who've survived COVID-19 ought to be our best hope here.
The first monoclonal antibody was approved by the FDA in 1986 for kidney transplant rejection.
That antibody was based on murine hybridoma technology, which was invented a decade earlier.
Murine meaning mice.
First, researchers injected mice with an antigen, which is a substance
that causes the body to make an immune response.
Then they isolated B-cells from the spleen, and fused those B-cells
with myelomas, or cancerous plasma cells.
This creates hybridomas that produce antibodies like B cells but replicate
with the longevity of tumor cells.
Hybridomas can be grown in culture,
with each culture producing a single antibody targeting one specific antigen,
hence monoclonal.
And this allowed researchers to select the antibody
with the right specificity, and then to mass produce it.
Monoclonal antibody production has advanced a lot since the 80s,
but it still follows those basic steps: you isolate antibodies against a particular antigen,
select the best one to three candidates, and then produce a lot of them.
And while some researchers still use mice to derive antibodies,
the most popular method being deployed right now for the SARS-CoV-2 virus is to look right
in the blood of recovered patients, an approach
that was still aspirational less than a decade ago.
Essentially all research groups are focusing their efforts on antibodies that bind
to the infamous "spike," a well-exposed protein on coronaviruses
that facilitates viral entry and that everyone loves to draw.
The majority of these antibodies target the receptor binding domain of the spike,
which docks into the ACE2 receptor on human cells.
An antibody that binds somewhere along its 168 amino acids would have a good chance
of neutralizing the virus.
The blood of one recovered patient would most likely have multiple unique antibodies that bind
to the spike and the receptor binding domain.
However not all of these would be equally potent, last long enough in blood or fare well
in the mass manufacturing process.
So the companies developing monoclonals need to select the best candidates using a variety
of in vitro and in vivo techniques.
The good news is that more than a dozen companies are already past this stage.
Some are going ahead with one carefully-chosen antibody, while others are choosing a cocktail
of antibodies, which might provide extra insurance
that the virus will not escape, or mutate away, from the drug.
So which patients would be the best candidates to receive this type of drug?
Well a monoclonal that is safe and effective could definitely work to reduce progression
of COVID-19, especially if given early.
But an intriguing idea is to use monoclonals as a sort of temporary vaccine, especially in those
at higher risk of exposure, like essential workers.
And monoclonals that effectively prevent infection could be especially useful
for vulnerable people who are at higher risk of developing severe
or fatal disease; like nursing home residents.
We have many nursing homes that are just suffering enormous trauma from this virus.
And we might be able to go to a nursing home, and give everybody in the nursing home,
right now, a dose of, a cocktail of monoclonal antibodies, preventing infection.
Vaccines might not work so well in older patients, and they take a while to work.
So in the middle of an epidemic, a vaccine is less attractive than a monoclonal antibody.
Of course a monoclonal antibody is not a replacement for a vaccine.
Monoclonals would be effective for a few months;
up to 3 or 4 if they have a naturally long half-life
or have been modified to extend the half-life.
Protection from vaccines is more long-lasting.
At least a year, and typically years, plural.
But in the setting of a pandemic, monoclonals do have an important benefit over vaccines.
Trials for monoclonals are much faster than they are for vaccines.
Vaccine studies that are planned are, like, 20, 30 thousand patients.
But monoclonal antibodies, there's a lot of reasons we can do much smaller trials,
and learn a lot really quickly, especially in places where the attack rate is really high.
In the right clinical trial, we will be able to tell pretty quickly, within months,
whether there's a benefit or no benefit.
There are a lot of things about these drugs we don't know yet;
for instance what is their bioavailability in tissues affected by COVID-19;
if the virus might mutate away from them, or what kind of adverse events they might cause.
But the upcoming trial results-- whether promising or not--
will be crucial in deciding the course of this pandemic before a vaccine hopefully arrives.
So look out for news over the coming months, since results from these trials will roll
in as soon as August and continue through the fall of 2020.