Cancer researcher Catriona Jamieson is sending tumors into space

What happens when you catapult cancer into space? Or shoot stem cells toward the stars?

Catriona Jamieson, a hematologist and director of the Sanford Stem Cell Institute at the University of California, San Diego, has done both. Through collaborations with organizations like NASA, her lab has sent tumors and stem cells aboard private spaceflights like SpaceX CRS-24 and the recent Axiom-3 mission to be studied in the International Space Station.

On Earth, Jamieson sees patients with bone marrow diseases, including myeloproliferative neoplasms and leukemia. Her research aims to understand why, as stem cells age, they develop mutations that make them cancerous or precancerous. And low Earth orbit, she found, offers her a chance to investigate the mechanisms behind cancer growth on an accelerated time frame.

She sat down with STAT to discuss oncology in orbit, the intersection of the private space industry and the drug development pipeline, and her thoughts on a literal “cancer moonshot.” This interview has been edited for length and clarity.

You’re a hematologist studying leukemia. Where does space fit in with your work?

I was reading the NASA twin study that was published in Science in 2019. It showed that Scott Kelly, after 340 days in space, came back 2 inches taller than his brother Mark, who is an identical twin. I thought, “Well, that’s great, we can go to space and be 2 inches taller. That’s not too bad!”

But then I noticed he had inversions and translocations in his chromosomes. His chromosomes were kind of mixed up in the immune cells, which can happen if you have preleukemic conditions developing in your blood, so that doesn’t look good. Then he had evidence of activation of telomerase, which can be associated with the stem cells now becoming premalignant, or in other words, precancerous. I thought, maybe space is a way to understand stem cell aging when it starts to be premalignant and fully malignant but in an abbreviated time frame. That’s what we started to do.

What was the first space mission you were involved with, and what did you launch into space?

Our first mission was SpX-24 in December of 2021. This was in collaboration with NASA. They gave us a $5 million grant to start the world’s first integrated space stem cell orbital research lab, ISSCOR. The first mission we did together with our implementation partner, it’s called Space Tango, was to send these little mini-bioreactors. They’re like little pediatric blood bags that have a three-dimensional sponge inside. We seeded that with bone marrow that comes from people undergoing hip replacement that were kind enough to donate their bone marrow.

We put the bone marrow in those little nano-bioreactors, and we tagged them with a reporter, a fluorescent signal that tells us are those cells asleep or are they dividing? We want our normal bone marrow stem cells to be asleep 80% of the time to maintain their full fitness, their full potential to clone themselves. If they lose that, then they become exhausted.

Our first mission, SpX-24, showed that actually stem cells get exhausted in space. They go crazy, they party, they hyper-proliferate, and then they lose their capacity to go to sleep. They’re totally wired. Then they lose their functional potential.

We thought, can we do this again? We did it four times: SpX-24, 25, 26, 27. This was with different bone marrow donors [of different ages]. Compared with ground controls, they all aged too quickly. They shorten their telomeres and they started to show stress responses.

Sounds like a bad thing, right? What does that mean?

It’s not a good thing. In the 30 days that the stem cells were in space, in the first couple of weeks, they were fine. The stem cells are OK with a marathon, but if you subject them to an ultramarathon — which is exposure to space for 30 days — they really start to lose functional capacity.

What that means is it’s possible astronauts would age too quickly, at least in their stem cells, if they go to space for too long. Maybe short bursts are OK, but if you go for 30 days or more, maybe that’s the limit. Maybe we need to do something to allow their stem cells to recover when they come back.

So we started studying the astronauts. Private astronauts were going up on the Axiom missions. We sent our first tumor organoid payload up on Axiom-1 in 2021. The astronauts said, “Hey, we want to help with this experiment. We’re going to get our blood cells [examined], and you can take the stem cells out of the blood and measure, ‘Are we aging too quickly in our blood stem cells?’” We’ve been doing that with Axiom crew members and that’s been very exciting.

Was that the first time we’ve launched tumors into space?

Axiom-1 was the first time human tumors had ever been studied in space. We used that little nano-bioreactor, the little pediatric blood bag, but this time we put in tumor organoids. We had ones for colorectal cancer, leukemia, and then triple-negative breast cancer. We labeled the colorectal cancer and leukemia with a cell cycle reporter that tells us if the cells are proliferating or dividing too much. In the triple-negative breast cancer and leukemia, we put in that cancer cloning gene reporter that measures ADAR1.

We can track cancer when it starts to clone itself based on this one gene called ADAR1 — which is “on our radar.” We saw that in mouse models, but also in these little mini-bioreactors, and we can also track if the cells are proliferating. … We were able to see that [ADAR1] gets turned on in space. That is something we see over time in people who have cancers, we just see it happening more quickly in space.

How much faster is this occurring in space, and is it concerning?

It is concerning. In terms of tumor growth, we see tripling in growth of these little mini-tumors in just 10 days. If that were to happen on the ground, that would take a year to 10 years, depending on the type of cancer. It means [space is] abbreviating the time frame. The cancer’s just taking off like a rocket, it’s just blasting off.

I thought, “That looks kind of dangerous.” Jessica Pham, who’s my lab manager, said, “Let’s stop it in its tracks. Let’s see if we can slow it down.” And so we’ve been making a blocker, a cancer kill-switch that we call rebecsinib.

Jessica said, “Let’s test it in space,” and I said, “Well, that’s ambitious.” [Rebecsinib] worked in Axiom-2 against triple-negative breast cancer organoids. It was more effective than another drug that we think is an ADAR1 inhibitor, called fedratinib. We thought maybe that was just a one-off with just one mission, so we just did it again a couple of months ago with Axiom-3. Same thing. Rebecsinib is a cancer kill-switch. It’s a potent blocker of cancer growth. If you’re not growing, you’re dying. … This is a pretty potent drug that we’re trying to get into the clinic by the end of this year.

But what about using space as a place to study how cancer evolves in an accelerated time frame so we can test multiple drugs? That, we think, is a literal cancer moonshot. So when Joe Biden coined that term “cancer moonshot,” I’m not sure he was thinking of literally doing this in space, and nor were we. But it just happens to be a brilliant idea.

A “literal cancer moonshot,” I like that. Where are we right now with the research, and what comes next?

We’re setting up to do Axiom-4. We plan to send the cancer cells from people who have metastatic cancer, again with that ADAR1 reporter, but also with cells that we think are feeding the cancer: our own stem cells. The normal stem cells, we think, are recruited to the cancer thinking it’s an injury and it’s trying to fix it, but in fact it’s feeding it. We’re going to look at that and see if we can block that interaction that we think is predicated on ADAR1 by using the drug recansinib and another drug called fedratinib. … If we genetically knock down ADAR1, do we block cancer’s capacity to clone itself?

What’s so special about the stem cell lab you have on the ISS some 250 miles above Earth that’s giving you these interesting results? Is it the microgravity? The radiation?

I’m so glad you asked that because when we first went up, we thought it was radiation. Nope! It’s 1.5-fold more radiation than on Earth. So that’s not enough to cause these changes.

It looks like microgravity. When the cells come away from each other and the matrix is not as stiff, the cancer stem cells start to say, “Hey, this is great. We can clone ourselves. We’re not restricted by anything stopping us.”

Why would that be relevant for Earth? The stiffness of the tissue can actually determine how well cancer grows. We’re starting to see that in space just a little bit more quickly.

Also for stem cells being able to feed a tumor on Earth rather than in space, we have what’s called a fight-or-flight response. We’ll mobilize our stem cells in response to stress and so we get the stem cells going to tumor sites in response to stress. Microgravity does that too. It basically initiates the fight-or-flight response.

The third thing we’ve seen in space that I think is really essential fundamental cancer biology is the activation of human endogenous retroviral sequences, HERVs. That happens in tumors on the ground, but it just happens faster in space.

What has surprised you the most about studying tumors in space?

I think the surprise is how illuminating space is. I didn’t know how different things would be in space, that it would be an accelerant for understanding essential human biology, like normal stem cell aging under conditions of stress, or cancer evolution under conditions of stress. It recapitulates stress in a way that compresses the time frame. It’s like the theory of relativity, you get this compression of time so you’re able to see these things faster.

Pharmaceutically speaking, what sort of precedent does your research in space set?

This is the first time space has ever been used in the development of a drug for cancer. Period. Full stop. That is unique.

[Now, we can ask,] “Could we make drugs more effectively, actually, in space?” We know we can do protein crystallography more effectively in space. Big companies have used that for protein crystallization. But I think the active pharmaceutical ingredient development process could be accelerated by space as well.

People might say, “But that’s way too expensive.” But it isn’t. These experiments have saved us so much time. It’s saved us money. The big challenge was getting the payload back. Now, with Sierra Space launching the Dream Chaser in the next couple of months — which is the first space plane that is going to launch on a rocket, but then land on any runway that takes a 737, like hopefully the one here in San Diego — we can get the products back from space and have them right in the lab within just an hour or two.

Axiom Space is building the world’s first commercial space station, which will likely be up and running by 2026. That is really exciting because they can help develop cellular therapies, biologics, and small molecules to block all of these properties like cancer development and accelerated stem cell aging … in space and then bring the products back. So the whole environment has just taken off, pun intended.

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