News | Sanford Stem Cell Institute at UC San Diego

Tumor Organoids in Microgravity

The results of this spring’s International Space Station-based research will help shape the next phase of experimental rebecsinib access on Earth

Rebecsinib — an anti-cancer drug developed by UC San Diego Sanford Stem Cell Institute Director Catriona Jamieson, M.D., Ph.D., and her team — is “go for launch.”

The U.S. Food and Drug Administration this spring green-lit the experimental therapeutic for a Phase 1 clinical trial, making it the first and only ADAR1 inhibitor with an approved investigational new drug application. Under it, as many as 66 patients with relapsed or refractory secondary acute myeloid leukemia or higher-risk myelofibrosis will be granted access to the medication, on an experimental basis.

Clinical trial aside, the drug itself is also “go for launch,” ready to rocket to the cosmos for further testing aboard SpaceX’s Axiom 4, scheduled to launch around Memorial Day from Cape Canaveral, Florida.

"We're thrilled to take this drug from the bench — and a bench on the International Space Station, even — to the bedside of patients who need it most,” said Jamieson, a leading stem cell biologist and board-certified hematologist with broad clinical expertise in caring for patients with blood cancers.

Approximately 40% of people will be diagnosed with cancer in their lifetime, according to the U.S. National Institutes of Health’s National Cancer Institute. A sizable percentage of cancer deaths are due not to the onset of the disease, but to recurrence and spread — which rebecsinib appears to halt in space-based experiments, in cancers linked to the gene ADAR1. That means the drug could help pave the way to diminishing the deadly disease into a single, manageable health event.

"Rebecsinib shows all the promise in the world not only to halt the progression of multiple cancers, but to shrink them, as well as prevent their spread to other sites in the body,” she added.

New drug holds promise for 18 additional cancer types

Astronauts aboard Axiom 4 will test the efficacy of rebecsinib on tumor organoids derived from the cancer stem cells of consenting patients with secondary acute myeloid leukemia, metastatic ovarian cancer, metastatic breast cancer and glioblastoma multiforme.

The hope is that the investigational new drug prevents the miniature tumors from growing, as it did on Axiom 3 with cell line-derived triple negative breast cancer tumor organoids. On that mission, completed in early 2024, the small molecule inhibitor acted as a sort of "cancer kill switch" by halting the growth of ADAR1-expressing breast cancer organoids.

Back on Earth, rebecsinib’s Phase 1 clinical trial will begin sometime this year at the UC San Diego Moores Cancer Center, for patients with high-risk myelofibrosis or secondary acute myeloid leukemia. The results of this spring’s experiments with the drug aboard the International Space Station — dubbed “Cancer in Low Earth Orbit (LEO)-3” — will rapidly inform the development of a Phase 1b/2 study by highlighting susceptible tumor types in space, where cancers triple in size in 10 days — a process that could take 10 years terrestrially.

Ideally, rebecsinib will be available to all patients with high-risk myelofibrosis or secondary acute myeloid leukemia in a couple of years. The Phase 1 clinical trial, however, is only the beginning. The drug holds promise in fighting 18 additional types of cancer, including triple-negative breast cancer and any cancer that involves ADAR1 in its development and progression.

Different interstellar experiment focuses on aging

Jamieson’s team is leading another scientific investigation aboard Axiom 4: Space Associated Stem Cell Hallmarks of Aging (SASHA) in Astronauts, which will focus on how space travel affects blood stem cell aging. Specifically, it will examine the roles of two enzymes, APOBEC and ADAR1, linked to inflammation, stem cell aging and pre-cancer initiation.

By studying how these enzymes affect stem cells and the acquisition of mutations during spaceflight, SSCI’s Sanford Integrated Space Stem Cell Orbital Research (ISSCOR) Center team will augment findings from two prior missions, rounding out essential insights into accelerated stem cell aging under conditions of extreme stress. Insights gained from the SASHA study will provide valuable data on aging and inflammation, key factors in many diseases.

The experiments are made possible by a $2 million grant from NASA — via its In-Space Production Applications program — to Jamieson's company, Aspera Biomedicine, and SSCI, which will receive $1 million.

In low-Earth orbit, the weak pull of gravity — also known as microgravity — places cells under incredible stress and promotes inflammation, causing an accelerated version of a process that resembles aging. When scientists send organoids — miniature versions of cancerous tumors or organs created from human stem cells — to space, each month can provide a preview of several years of disease development and progression, as well as drug efficacy.

The environmental stress and inflammatory cytokine signaling caused by microgravity also accelerate ADAR1 activation in malignancies. Because of this, microgravity offers Jamieson's team a unique opportunity to expeditiously determine rebecsinib's efficacy against different types of cancer. It also affords the opportunity to establish methods for protein crystallization and oral formulation.

Jamieson received the prestigious International Space Station National Laboratory 2024 Compelling Results Award in Biology and Medicine — for her discovery that rebecsinib blocks the activation of ADAR1 in cancer — last summer.