March 31, 2020

Deconstructing Rudy Giuliani ‘stem cells for COVID-19’ podcast & NK cell transplant idea

Deconstructing Rudy Giuliani 'stem cells for COVID-19' podcast & NK cell transplant idea

Deconstructing Rudy Giuliani 'stem cells for COVID-19' podcast & NK cell transplant idea
Robert Hariri talking with Rudy Giuliani on testing “stem cells” for COVID19.

Rudy Giuliani has been tweeting all kinds of wild things about the novel coronavirus and is apparently very excited about the idea of “stem cells” for COVID-19 patients.

What could go wrong, right?

Deconstructing Rudy Giuliani 'stem cells for COVID-19' podcast & NK cell transplant idea
Dr. Robert Hariri of the biotech Celularity talking with Rudy Giuliani on testing “stem cells” for COVID19, a podcast more focused on the idea of using NK cell transplants for the novel coronavirus disease.

Giuliani starts vaguely tweeting about “stem cells”

I wrote a few days ago about how Giuliani had been plugging an upcoming podcast he was doing on “stem cells” for COVID-19. Since then I watched the video so you don’t have to, that is unless you really want to for some reason. In that case, I’ve pasted the YouTube video further down in this post.

At the time Giuliani was still plugging the upcoming podcast but hadn’t posted it, it wasn’t clear what that interview was going to be all about and who it would be with exactly. In fact, it was possible it wasn’t even going to be about real stem cells.

At first before we had such details, I wondered if he was going to be interviewing an unproven stem cell clinic person or someone in that sphere like a clinic supplier. For that reason and because the general idea of stem cells for COVID-19 has caught fire in not entirely positive ways, I was wary of the upcoming podcast.

Now we know Giuliani interviewed Dr. Robert Hariri of the biotech Celularity, which has been focused on placental cell derivatives mostly for cancers like glioblastoma. Celularity originally caught my eye a couple years back because it was generating some buzz in the media and had raised hundreds of millions of dollars. I also was struck by the huge aspirations of the company itself such as trying to extend human life by decades.

The core biomedical idea here

Based on Giuliani’s interview with Hariri, what are Celularity’s COVID-19-related plans? The podcast wasn’t so much focused on a direct stem cell therapy, but on trying to repurpose the firm’s investigational natural killer (NK) cell therapy called CYNK-001 originally developed for cancer for use for COVID-19 instead.

The hypothesis seems to be that many of the patients who get the sickest from the novel coronavirus may have a deficiency in NK cells. This idea is mostly based on one small COVID-19 paper and on past limited data suggesting amongst SARS patients that those who got the sickest sometimes had fewer NK cells.

Remember that in a general sense NK cells are immune cells that have important, unique roles in killing both cancer cells and cells infected with viruses.  The populations of NK cells, which are specialized lymphocyte lineage cells, in the placenta may also help protect the fetus from maternal infections, a fundamental concept for Celularity as a company.

The notion of an NK cell treatment for COVID-19 is interesting and worth consideration, but at the same time in my view there’s not much data behind it yet so it’s very early days. There’s much we don’t know. For instance, the Celularity placental allogeneic NK cell product just might not work in this context even if some other NK cells could. The different, but related idea of designer NK cells engineered to home in on SARS-CoV2-infected cells is pretty cool, yet that kind of thing could take a while to make, preliminarily testing, etc. and time is short in a deadly pandemic.

Politics and some eye bulges

To set the stage of the interview, Hariri and Giuliani were sitting across from each other, both with suits adorned by American flag pins. Not that there’s necessarily anything wrong with that, but Hariri had also around that same time been tweeting some rhetoric at POTUS and others that seemed unusual in tone to me. For instance, to me it seemed that his tweets were in part pushing for less regulatory oversight. In addition, he tweeted in a positive way to a stem cell clinic operator, which for me at least wasn’t a positive. Below is one of his tweets toward Trump before the podcast aired.

In the terms of the podcast itself, I couldn’t help but notice as I was watching the Hariri interview that Rudy has a habit of bulging his eyes outward and interrupting his guest at key moments so that kind of stuff is distracting. For instance, at one point it seemed that Hariri was trying to start to say something like, “We’re fortunate we have a President…”, but he’s then interrupted so it’s hard to be sure if that was going to be a reference to Trump.

Giuliani mentions stem cell clinic-like offerings as context

As the discussion got going more, the former mayor gave some background related to stem cell clinic-like offerings and talks glowingly about it, such as that it was recommended to him by former Yankee pitcher Mariano Rivera and by his own son who’s a pro golfer with “very good results”. There was also some mention of Tiger Woods’ knee. So that wasn’t a reassuring context to start the interview.

The chat mentions in a general sense that there are supposedly minimal adverse effects of cell therapies and there was a claim that generally cellular therapies are “quite safe.” These statements are not things one can just broadly assume. We should keep in mind again too that what Celularity is wanting to test is an NK therapy (I think which is derived from placental stem cells), not actual stem cells.

More details & perspectives on Celularity’s NK COVID-19 plan

From the interview, the plan seems to be that if an IND for this (submitted by Celularity around March 3) is approved, which I think is likely, that they will infuse 50 patients. It was less clear if there will be a 50-patient control group or rather if the 50 mentioned would include 25 controls and 25 infused with NK cells.

Hariri was upbeat about the prospects, saying something along the lines of, “I’m pretty confident the safety is going to be more than acceptable …and we’re going to boost the immune response” in the COVID-19 patients. Based on the limited amount of relevant data available that latter part especially seems like a long shot to me, but I hope he’s right and that I’m wrong to be skeptical. Note that I’m not a physician or immunologist.

There are potential patient risks here too with an NK cell approach such as increased respiratory inflammation due to NK cells potentially attacking massive numbers of patient cells in the respiratory system or elsewhere. While the Celularity NK cells have seemed safe so far in cancer patients, which is encouraging in a general sense, that doesn’t mean they are for sure safe for patients who have had serious coronavirus infections for weeks.

One other thing making me somewhat skeptical about the Celularity plan is the timing. I would have expected endogenous NK cells to have an earlier role in the pathogenesis of COVID-19 so giving an allogeneic NK product late in the course of the disease seems counterintuitive and could pose unique risks.

Then Giuliani brought up the whole Trump-plugged Z pack/hydroxychloroquine thing that has raised concerns in the biomedical community. At that point while watching, I wondered how Dr. Hariri would handle this. Be cautious? Jump right in? He didn’t endorse the Z-pack idea or criticize it, but instead he ended up comparing Celularity’s NK therapy to the Z-pack approach in terms of purported shared big-picture mechanisms.

Looking ahead

Why did Hariri sit down with someone as controversial and politically-charged as Giuliani?

To try to connect with Trump, who might then go on to mention this stuff at a press briefing or on Twitter? To put political pressure on the FDA regarding his IND? Raise funds for his company?

What if Trump ends up vaguely encouraging the world to try “stem cells” for COVID-19 because of Giuliani’s advocacy here? That could do so much harm.

In general, it’s a tough judgment call during a pandemic about what should be tested in the way of investigational therapies in patients and what shouldn’t.

Also, how much evidence should be required before pulling the trigger to go into patients with a new product during an outbreak that is killing tons of people? Note that the FDA just approved the Trump-promoted anti-malarial drugs hydroxychloroquine and chloroquine for COVID-19 based on little evidence.

Going on Giuliani’s podcast was a calculated risk for Hariri. What’s your reaction to it?

In the bigger picture, what do you think of the Celularity NK idea for coronavirus patients?

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