As the COVID-19 death toll continues to climb, Washington University researchers are testing whether lab-engineered proteins known as monoclonal antibodies can be used to treat the illness.
Though monoclonal antibodies have been used for decades to treat a variety of ailments, including cancer and arthritis, the pandemic has propelled these synthetic immune molecules into the spotlight. Results from early trials indicate certain antibodies can reduce the severity of COVID-19 in patients, but researchers say there’s still work to be done before a drug is ready for market.
For the uninitiated, the process of producing lab-grown antibodies can look a bit like science fiction.
Inside carefully controlled steel tanks, animal immune cells, often from mice or hamsters, grow in a warm nutrient slurry and create copy after copy of the antibodies. These synthetic antibodies are modeled after human antibodies collected from the blood plasma of patients who recovered from COVID-19.
The molecules function like an actual antibody, attaching to the halo of barbed proteins on the outside of the coronavirus and blocking it from infecting human cells — at least, in the lab.
Researchers nationwide are now working feverishly to test whether the experimental treatment works on COVID-19, in essence, supercharging patients’ immune response by infusing their blood with antibodies designed to target the coronavirus.
One question, said Washington University infectious disease specialist Dr. Rachel Presti, is whether monoclonal antibodies can keep newly infected COVID-19 patients from getting sicker.
“What we're looking for is mainly, can we keep people out of the hospital?” said Presti, an associate professor of medicine. “But also, how long do they have symptoms? How quickly do they get better?”
Presti is leading a series of clinical trials in St. Louis to test whether monoclonal antibodies produced by pharmaceutical giants Eli Lilly and Regeneron can reduce the severity of COVID-19 symptoms among patients.
In one trial, patients hospitalized with more severe cases of COVID-19 will receive either a “cocktail of antibodies” or a placebo to see if the treatment helps them recover faster. Eli Lilly released preliminary results in September from a clinical trial of 452 patients with COVID-19, showing that 1.7% of those who received an experimental antibody treatment were hospitalized, compared to 6% of patients who received a placebo.
A ‘stopgap measure’
A separate study at Wash U will test whether a blend of two antibodies developed by Regeneron can prevent infection in those who have been recently exposed to the virus by a sick household member.
Because it will likely be months before a coronavirus vaccine is ready for market, a treatment that provides some measure of protection against the virus could be a valuable tool.
But even if monoclonal antibodies can successfully block infection, Presti said, they’re only a temporary solution. Unlike a vaccine, which causes your body to produce its own immune cells, a dose of synthetic antibodies circulates in the blood for no more than a few months before dissipating.
“A vaccine is better than passive transfer of antibodies because your immune system now knows how to respond,” Presti said. “[It’s] not somebody else's immune system that you're borrowing.”
Marion Pepper, an immunologist at the University of Washington, calls monoclonal antibodies a “stopgap measure” until a vaccine is produced.
The urgency of the pandemic, she adds, pushed biomedical researchers and companies to quickly identify a handful of antibodies that could be used as the basis for these experimental treatments — but that doesn’t necessarily mean these are the best candidates.
Pepper is part of a team focusing on older antibody-producing immune cells, which get progressively better at binding to the coronavirus protein spikes, on average. The group has identified several potent antibodies, but Pepper said they may be at a disadvantage, compared to front-runners from Lilly and Regeneron that are already in clinical trials.
“It's a double-edged sword, because you're trying to get good therapeutics out as fast as you can,” Pepper said. “But there's a chance that you're going to get better antibodies if you wait.”
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