In the past decade, chimeric antigen receptor (CAR) T cell therapy, which leverages a patient’s engineered immune cells to fight tumors, has shown promise in cancer immunotherapy. But the behind-the-scenes steps of how these therapeutic cells are made and then get back to the patient receiving the therapy are not simple.
The journey of CAR T cells begins in a hospital room, where doctors draw the patient’s blood cells.1 These cells then travel to manufacturing facilities where they undergo genetic modifications to recognize and attack specific cancer cell markers, before being shipped back to the patient for therapy. However, throughout this journey, the delicate cells must be handled with care.
Gloria Elliott is the program manager for the BioSystems Stabilization project.
Courtesy of ARPA-H
“It 's not like putting it in in a FedEx envelope and sending it,” said Gloria Elliott, a biopreservation researcher who is now a program manager at the Advanced Research Projects Agency for Health (ARPA-H). The cells must be shipped in liquid nitrogen and endure multiple rounds of freeze-thawing at the hospital and manufacturing facilities.
“All of this is just really logistically cumbersome. It adds $20,000 to $30,000 to each dose. But the bigger cost of all is the risk,” said Elliott. Logistical snags, such as shipping delays or freezer failures could prevent the product from being created or reaching the patient in time. “That lost product is a lost life.”
To circumvent this problem, ARPA-H has invested in a BioStabilization Systems (BoSS) program, which will likely begin this fall. As part of the project, scientists aim to apply nature-inspired preservation strategies to biologics, enabling these therapeutics to be stored at room temperature. Eliminating cryopreservation requirements could lay the foundation for simplified logistics and improved access to life-saving products like cell and gene therapies.
The Costly Vulnerability of Keeping Biologics Cold
An increasing number of people rely on biologics such as vaccines and drugs that need to be maintained at low temperatures. “Currently over 150 million Americans [are] using some kind of thermally unstable biologic,” said Elliott. These range from routine drugs like insulin to specialized ones like CAR T cells, amounting to billions of dollars spent each year in maintaining cold chain logistics.
This dependence on cryopreservation renders stakeholders—including researchers, doctors, manufacturers, and patients—vulnerable. “We see this all the time when there are power outages or some kind of manmade or natural disaster,” said Elliott. “Reports start coming out of people…losing their 90-day supply of insulin or immunotherapy. It’s already expensive, and they certainly can’t afford to lose that product.”
Gloria Elliott and her team addressed potential proposers about BoSS project’s scope during the Proposers’ Day event held in January 2026.
ARPA-H
The cost as well as the risks of relying on cold preservation prompted ARPA-H to look for alternatives. “We’re saying forget cryo[preservation], let’s look for solutions that enable us to put things on the shelf at ambient conditions with no freezing whatsoever,” said Elliott. This means that for material requiring the coldest preservation temperatures, like those stored in liquid nitrogen, there would need to be an almost 200°C leap in storage temperature, she explained.
Nature-Inspired Preservation Techniques
The reason Elliott and others think this change is possible is because several animal species have evolved ingenious ways to protect their cells and molecules from temperature and other environmental stressors.
For instance, a cell line derived from the midge Polypedilum vanderplanki can survive in a desiccated state at room temperature for nearly 250 days.2 When researchers dug into how this was possible, they found clues in morphological and physiological adjustments, such as fragmentation of the endoplasmic reticulum or reduced mitochondrial respiration, that potentially help the cells survive the stress.
Investigating the molecular mechanisms behind these adaptations has further revealed that intrinsically disordered proteins work together with internal cellular chemicals to protect the cells from desiccation.3 According to Elliott, these findings offer crucial chemical and molecular clues to reorganize cellular contents to render the cells durable.
Scientists have learned from microbes as well. Studying bacteriophages that survive at room temperature for extended periods of time has offered insight into physical material that enables this behavior, offering clues into potential formulations that could render materials thermostable.4
According to Elliott, scientists working in the BoSS program will harness such strategies to test the feasibility of storing biological materials at room temperature. However, some of these approaches would involve delivering materials into cells to render them stable. “A lot of the molecules we like to use in the cell are not easy to put into the cell,” said Elliott.
Looking at the shape of cultured cells has offered some clues into overcoming this problem. For example, a couple of years ago, researchers found that rectangular fibroblasts were more amenable to taking up large molecules through the formation of pores after exposure to ultrasound waves.5 Elliott noted that studying such systems could help researchers design better technologies to reversibly deliver cargo intracellularly.
“If we study nature well enough, I think we [will] have the answers,” said Elliott. “Nature can do it, so there's no physics that should be preventing us from doing it.”
- Wang X, Rivière I. Clinical manufacturing of CAR T cells: Foundation of a promising therapy. Mol Ther Oncolytics. 2016;3:16015.
- Belott CJ, et al. Membraneless and membrane-bound organelles in an anhydrobiotic cell line are protected from desiccation-induced damage. Cell Stress Chaperones. 2024;29(3):425-436.
- Kc S, et al. Disordered proteins interact with the chemical environment to tune their protective function during drying. Elife. 2024;13:RP97231.
- Coleman HJ, et al. Formulation of three tailed bacteriophages by spray-drying and atomic layer deposition for thermal stability and controlled release. J Pharm Sci. 2024;113(11):3238-3245.
- Baig MA, et al. Influence of cell shape on sonoporation efficiency in microbubble-facilitated delivery using micropatterned cell arrays. Sci Rep. 2024;14(1):30845.
