“One of the things that this pandemic has I hope taught all of us is that science really matters,” declared E. John Wherry, Ph.D., of the University of Pennsylvania, during the Cancer Research Institute (CRI) COVID-19 live stream event on June 18. “We're going to get out of this mess because of science.”
Specifically, we will need immunology, the science of the immune system, to address COVID-19, the disease caused by the SARS-CoV-2 coronavirus that continues to spread across the globe.
Recent advances in cancer immunotherapy research are propelling some of the most promising efforts to address COVID-19, and so CRI brought together three esteemed immunologists—Carl H. June, M.D., Miriam Merad, M.D., Ph.D., and Wherry—along with STAT'’s Matthew Herper to discuss where we are now and how move forward.
“Over the past ten years, the cancer immunotherapy field has built the ability to profile the immune system in exquisite detail to try to match therapies to the right kind of patient,” said Wherry, an associate director of the CRI Scientific Advisory Council and the director of UPenn’s Institute for Immunology.
“We can measure the immune system with an unprecedented level of specificity and detail… and integrating the ability to use information about the overall immune health of the patient to tailor treatments… might be beneficial in diseases like COVID-19,” Wherry shared.
As the director of the Precision Immunology Institute at New York City’s Icahn School of Medicine at Mount Sinai, Merad has been applying her knowledge of immunology at “the epicenter of the epicenter.”
“At some point in our hospital we had 2,000 patients. Our hospital became a COVID hospital. We had stopped all elective surgery. It was really quite bleak.”
Merad, who received the 2018 William B. Coley Award from CRI, has risen to the challenge despite not being an expert at coordinating real-time clinical responses.
“Researchers like to brainstorm and we think about it for months before we do an experiment,” said Merad. “Suddenly we had to go on the front line together with the clinicians because they were saying, ‘we need your help.’”
Fortunately, Merad and her team did have some groundwork laid through their prior efforts in cancer immunology. “Clearly, COVID-19 is a very heterogenous disease,” she said, referring to how the coronavirus can affect different people in very different ways.
“Cancer immunotherapy groups were quite prepared,” according to Merad. “We think about heterogeneity all the time… trying to understand why some patients respond and why some do not.”
Some patients who experienced severe COVID-19 appeared to be suffering from excessive inflammation, and characterizing this phenomenon was one of Merad’s first goals.
“What we wanted to know is how can we really predict and prevent the inflammation,” Merad explained. And her team developed a way to do that, “thanks to funding mostly from the cancer immunology agencies, including the CRI, that funded us over the years to really build this immune monitoring platform.”
“Suddenly we were able to measure inflammatory cytokines… and we saw this heterogeneity. We saw some patients had elevated inflammatory cytokine and some patients didn't.”
For these patients, an immune-suppressing treatment might be most appropriate. From the minimal data made public from one trial, one such drug—the steroid dexamethasone—showed great benefits for patients with severe COVID-19.
“I was astonished, actually, that that had happened,” exclaimed Carl H. June, M.D., the director of UPenn’s Center for Cellular Immunotherapies. As a pioneer of CAR T cell immunotherapy, June has extensive experience with a similar condition—cytokine release syndrome—that is associated with excessive inflammation.
“We have to be cautious, but our infectious disease specialists at Penn are going to put this into standard of practice from what I understood,” said June, a member of the CRI Scientific Advisory Council who himself got quite ill from COVID-19. “I'm really surprised at how fast they are willing to rapidly adopt that.”
“My bet is they may have just threaded the needle perfectly with a low dose at the right time in the infection. Assuming this can be confirmed.”
Merad echoed June’s caution.
“I would like to see the data… before we put something into practice,” she said. “I understand that everyone is anxious, but you know, we can be harmful to the patients.”
Regarding how ongoing immunotherapy treatments might affect some patients with COVID-19, Wherry noted that, “It's not clear-cut. There are some hints that maybe in lung cancer, PD-1 blockade may make things worse, but other data say that's just an effect of having lung cancer.”
In contrast to those with overactive immune responses, some patients’ immune systems don’t respond aggressively enough. As June summed up, “Some people need anti-inflammatories, others need basically their immune system to be jacked into action.”
As Wherry sees it, “The immune system is just one piece of the puzzle and we have to link that to other aspects of the patient's background, overall health, but we think about it as really part of immune health.”
To that end, all three experts agreed on the importance of improving our understanding of the immune system in order to address COVID-19, in addition to other diseases such as cancer and beyond.
The immune system remains “an untapped source of therapeutic targets,” Merad stressed. “There is so much we can discover still. It is really the beginning of a revolution where we can really learn from it and develop novel therapies. We need to invest in our understanding of the immune system and we need to harness it.”
Unfortunately, this pandemic has affected the scientific community’s ability to continue carrying on this important research. “There’s been a major, major impact on the scientific enterprise of the entire country,” said Wherry.
“A lot of that basic discovery work has essentially stopped. We can't restart on a dime. It's going to take a long time to rebuild what we have lost over the last few months,” he continued. “We have to figure out how to return to a really thriving scientific community as quickly as we can.”
“Now,” emphasized June, “is our opportunity to tell the public why they need science.”