Experiments aboard the International Space Station may offer promising advancements in fighting cancer
Getting seven experiments on the International Space Station requires a really good idea. Like a brand new way to attack tumors-one that you can only make in space.
Space has unique advantages for making medicines. Its very low gravity makes it possible to grow molecules in shapes and uniformity that are difficult to create on Earth. If they can be reliably and affordably produced, such molecules could have all kinds of novel uses in industry and medicine.
University of Connecticut engineer Yupeng Chen has been growing one such unusually rod-shaped nanoparticle, called a Janus base nanotube, on the International Space Station (ISS). The success of Chen's last five experiments has led to this latest $1.9 million award from the Center for Advancement of Science in Space and NASA's Division of Biological and Physical Sciences. With it, Chen and his colleagues will use the space station's unique environment to grow pharmaceuticals whose shape is their secret weapon.
During this mission, the team will grow Janus base nanotubes that carry interleukin-12. Interleukin-12 is a protein already produced naturally by the human body, but only in small quantities. It stimulates the development of helper T-cells, which recruit other parts of the immune system to kill invaders and cancer cells. Many tiny, incipient cancers are killed off by our body's interleukin-12 response all the time.
But cancerous tumors that become big enough to be noticed are clever. They often have ways to dampen the body's interleukin-12 response. However, delivering enough interleukin-12 could overwhelm the tumor's responses. The technique has worked well in the lab – so well that it has already been tried in humans. But there were some problems.
"Good tumor control, but the side effects in humans are very severe," says UConn School of Medicine immunologist Kepeng Wang, who is working with Chen on the project. During a past clinical trial, there was a tendency for interleukin-12 therapy to provoke fevers, flu-like symptoms, and other problems. Two people in the trial died. The results were clear. "You cannot inject the naked protein" into people, Wang says.
But perhaps you could inject it clothed.
Others have attempted to wrap toxic drugs inside of benign exteriors. Many of these efforts have involved nanoparticles: tiny roundish shells only a few hundred atoms or so across that can safely pass through the bloodstream until they get to their target. But round nanoparticles are too wide to get inside most solid tumors.
Solid, though, is something of a misnomer; tumors do tend to be less dense than healthy tissue. They have cracks and openings that a sufficiently small drug could sneak through. Most anti-cancer medications aren't small enough. Nanoparticles aren't generally small enough, either.
The super-skinny Janus base nanoparticles Chen's lab is working on are different. They can slip into the cracks and attack tumors from the inside. With cross sections of just 20 nanometers, they can also pass through the tiny windows between cells in the working area of the kidneys, and the openings in cartilage in the joints. Such skinny molecules could treat all sorts of disorders simply by getting to places other drugs can't.
They can also contain small molecules such as interleukin-12 within themselves, and then release them inside of a tumor. That would hopefully spare patients the severe side effects that occurred with naked interleukin-12.
Such specially shaped molecules would be game-changing, and manufacturing them in space has many advantages. For example, it's well known that crystals grow better in microgravity.
"They have more time to fill cavities and assemble, because there are no gravitational pressures. Since our nanotubes are self-assembled, there is a lot of similarity to crystallization. Without gravity, there's no sedimentation, the molecules can rotate and assemble freely, and make better structures," Chen says.
An astronaut works in the life science glovebox on the International Space Station to assemble the Chen lab's Janus base nanomaterials. (Video courtesy of NASA)
But manufacturing a drug in space has some special logistical challenges. Like getting into space – and getting back to Earth. The first time they ran experiments on the ISS, many of their samples leaked on the way home. They thought it was from the stress of space travel. But the problem was really with the ground transport.
"Splashing down into the ocean doesn't cause leakage," but bouncing around in a truck can cause leakage, says Trystin Cote, a graduate student on the team.
Now the samples are securely velcroed into styrofoam packing for the return trip to Earth. Works fine.
Communications with astronauts are also going well.
"As we watch live video streamed from the International Space Station workplace, we maintain constant communication with the astronauts; if they have any questions, they tell Axiom Space's Mission Control Operations personnel, who then relays the info to us, and vice versa," says Maxwell Landolina, a graduate student in Chen's lab.
This will be the team's seventh run of experiments on the space station. If it is successful, it might be the last one to depend on public funding. Chen's lab is working with Eascra Biotech, a UConn spinoff company, to commercialize the Janus nanotube manufacturing technique. The company was founded by Chen and his business partner, Ms. Mari Anne Snow. They're also working with Axiom Space, which is building Axiom Station, a private, commercial space station that will conduct extensive scientific research, technology demonstrations, and outreach engagements in the microgravity environment.
The team estimates that the additional cost of production of Janus base nanoparticle medicines in space will be only about $30,000 per kilogram. That would be about a hundred thousand doses, or about thirty cents per dose.
"In principle, that is not that expensive," Chen says.
This is a multi-million-dollar and multi-institute collaboration. Besides Chen and Wang, Mari Anne Snow from Eascra Biotech focuses on translating this technology into a product available on the market, and Dr. Lorenzo Deveza from Baylor Medical School and Dr. Susan Tannenbaum from UConn Health provide clinical expertise.
