COVID-19 and cell therapy: an interview with Daniel Weiss

Written by Freya Leask

computer-generated image of a virus

In this interview, conducted at ISCT 2020, Daniel Weiss, Professor, Medicine in Pulmonary Disease and Critical Care, University of Vermont (VT, USA) and Chief Scientific Officer, International Society for Cellular Therapy (ISCT), discusses the challenges of developing a cell therapy for COVID-19.

Why did you decide to kick the meeting off with an in-depth focus on COVID-19?

I think it’s inescapable. We’re living in a world that has been profoundly, probably irrevocably, changed by the COVID-19 pandemic. From a scientific standpoint, with respect to the ISCT, we’re certainly going to cover the range of topics that we would have covered anyway. However, as COVID-19 is on so many people’s minds, and has affected so many lives, personally and professionally, it just seemed like an important thing to start with.

It feels like every researcher looking at a potential therapeutic is pivoting or has pivoted to look at COVID-19, including cell therapy researchers. What would you say to researchers who are wondering about the focus of their research?

That’s an excellent question but it’s also a very broad question. The need for new therapeutics for COVID-19 is clear, since we don’t have a proven one as yet. It’s quite reasonable that anyone involved in any research discipline that potentially could be related to either the pathogenesis of the COVID-19 infection or developing a new therapeutic of whatever type might be considering shifting gears.

That’s bolstered by the fact that many, many funding agencies, from the National Institutes of Health (MD, USA), and the Department of Defense (VA, USA), to many nonprofit organizations globally, have allocated substantial funds towards COVID-19-based research. They hope to bring new understanding to the pathogenesis and bring together people with a wide range of expertise in related, and sometimes unrelated, disciplines. Therefore, this is an important time and it’s an important opportunity to bring the full strength of science towards COVID-19.

It also is a time where non-COVID-19-related research shouldn’t be completely left behind or left by the wayside. It’s critically important to try and maintain active research in other areas. Life and medicine must go on.

Has COVID-19 highlighted the fragility of the cell therapy supply chain and how you think that might evolve in the future?

Absolutely. We don’t need to look any further for inefficiencies and mismanagement in the way the United States has handled supply chain issues recently. There’s room for improvement in both of those aspects.

This is also a significant opportunity. Acute respiratory distress syndrome (ARDS) was a major problem prior to COVID-19 in terms of critically ill patients who end up on ventilators, and mesenchymal stromal cell (MSC)-based therapies were beginning to show clinical promise. This is based on a solid mechanistic understanding of what MSCs can and can’t do.

In the desperation for finding new COVID-19 therapeutics, cell therapy really has come to the forefront. Over the past several months, there’s been a significant increase in the number of both academic and industry-sponsored clinical investigations of predominantly MSC-based therapies for COVID-19. The results of these are still open, waiting for collection of proper data. One of the problems is that in the rush to do this, some of these investigations are being conducted in what would be considered sub-optimal ways, leading to issues that could potentially undermine potential success.

Unfortunately, you’re also seeing an expansion of illicit stem cell clinics out there offering unproven therapies for COVID-19, often focused on stem cell administration. Stem cell medical tourism was a problem prior to COVID-19; it’s one of the key focus areas of the ISCT and has unfortunately ramped up with the global pandemic.

With so many trials being started and so much research being published, how do you identify what is showing clinical promise?

This is a complicated question.

For trials, one should pay attention to those that have the appropriate approach and the best chance of truly showing the potential benefit. The first indicator of that is that the trial is regulated by an appropriate authority, for example FDA, in the United States, or EMA, in the European Union. The second is that the trial is conducted in a transparent manner, such that the source and biological attributes of the cells being utilized are clear and open.

Thirdly, and perhaps the most important, is that the trial has a control group. This includes patients who will receive a placebo in contrast to those who receive the actual study medication. This needs to be done in a randomized, double-blinded fashion so that neither the patient nor the caregivers know which treatment the patient is receiving.

It’s this type of well-proven, tried and true approach to therapeutic clinical investigations that will really show that MSC-based approaches are going to work. There have been a few initial publications, and certainly a number of press releases from different industry-sponsored investigations, in which a small group of patients were treated with the cell product itself. However, they were open label so that everybody knew the patient was getting the cells. The patients were followed and, in many cases, got better and survived. While that’s encouraging and thought-provoking, who’s to say they wouldn’t have survived anyway?

So all these guidelines exist; it’s just a case of ensuring we are following them in the excitement or panic of getting quick results?

From a human perspective, if your intensive care unit is full of COVID-19 patients and they’re not doing well, you of course will do anything possible to save those patients. We understand that.

Once you’ve figured it out a bit, you have to take that step back and say, we need to investigate a new potential therapeutic but we have to go by the rules that are well established. The ISCT has been trying to support and promote this mindset, in parallel with trying to stamp out the clinics out there that are just offering unproven things.

Why has much of the research and trials focused on ARDS as opposed to any of the other comorbidities of COVID-19, of which there are many?

There’s been ongoing research on all of these comorbidities but only some of them were immediately evident. For example, early in the pandemic, when patients were becoming quite ill and going into the Intensive Care Unit, they were predominantly dying from respiratory failure. However, that’s not to say there weren’t comorbidities such as cardiac toxicity or clotting issues. The natural evolution of understanding a disease is that is takes a while to appreciate everything that is going on simultaneously.

What questions do we still need to answer in order to treat COVID-19 better?

We need to learn more about the pathogenesis on a cellular and molecular level. This includes not just the cytokine storm but what else the virus might do to different cells, particularly those in the lung once the virus enters and begins to infect the cells. More fundamental understanding of these basic processes will help to guide the development of new therapeutics as well as support some of the therapeutics that are being considered at present.

An unexpected aspect is the sheer volume of literature already published on COVID-19 at this point. There are thousands of articles that have come out over the past several months and part of the challenge is to be able to wrap one’s mind around all these and try to make sense of it all.

From the ISCT perspective, we’re trying to promote legitimate therapeutics at the same time at the same time as eliminate the unproven therapies out there.

Disclaimer  

The opinions expressed in this interview are those of the interviewees and do not necessarily reflect the views of RegMedNet or Future Science Group.