ARPA-H’s BoSS Program Funds Three Teams Tackling Cold Chain Challenges for Cell Therapies

The Advanced Research Projects Agency for Health, (ARPA-H), an agency within the United States’ Department of Health and Human Services (HHS), recently announced awards and teams involved in its BioStabilization Systems (BoSS) program, an initiative that aims to develop new methods for producing, storing, and transporting cell-based biologic medicines at room temperature. ARPA-H has committed to provide up to $87 million across the four-year program. This round of funding will support Phase I of the program.

The teams have been tasked with pursuing new technologies that confer long-term, shelf-life stability to cell-based therapies and biologics making it possible to store and ship them without refrigeration. To accomplish this goal, BoSS teams will work across two technical areas. They will work on interventions to stabilize cells for storage and then reactivate them on demand as well as on creating novel processing systems that ensure these interventions are efficient and scalable for manufacturing. 

This week, members of the Reversible Ambient Temperature (RAB) team said that they have been awarded up to $7.3 million initially from ARPA-H. The RAB team includes representatives from Draper, a non-profit research, development, and manufacturing company, which serves as the administrative lead,and Likarda, a biotechnology company that develops hydrogel technologies for delivering and preserving cell therapies and biologics, which serves as the technical lead for the team. Other members of the team include scientists from CaseBioscience, CPSI Biotech, Fresenius Kabi, MiNK Therapeutics, and University of Colorado. 

For their part, this team will use AI-assisted design of experiments to optimize formulation, quiescence induction parameters, hydrogel composition, and recovery media as well as freeze-assisted droplet drying to achieve a stable product. Specifically, the RAB team’s biostabilization strategy, led by Likarda, will focus on simultaneous control of cell state, physical environment, and the cellular stress responses activated during freezing, dehydration, storage, and recovery. Meanwhile, the bioprocessing engineering team, led by Draper, will convert the manual steps of biostabilization into an automated, commercially viable workflow and will develop custom instruments to scale up the processes.

Likarda will contribute its proprietary Core-Shell Spherification hydrogel technology, which is designed to encapsulate and protect living cells while maintaining viability and function. CaseBioscience will provide expertise in clinical media formulation, biopreservation, and cellular metabolism to the development and evaluation of novel approaches for long-term ambient stabilization of therapeutic cells.

“The RAB team brings together deep expertise in cryoprotection, encapsulation, and cell state, with a focus on protecting cell viability throughout the stabilization and reanimation process, and the team has direct experience bringing products to market,” said Jason Fiering, distinguished technical staff at Draper. “Working in parallel, our interdisciplinary engineering team will develop the customized instruments needed to transfer these processes to clinical manufacturing environments.” 

In his comments, John Baust, PhD, an expert in biopreservation and collaborator on the project with CPSI Biotech noted that “the concept of preserving living cells in a dry state has been pursued for more than two decades, but significant scientific and engineering barriers have yielded limited success.” The BoSS program is an opportunity “to tackle this from multiple scientific and engineering directions simultaneously” that if successful “could represent a paradigm shift in how biologics are preserved, stored, and distributed.”

Other teams announced by ARPA-H include one led by DesiCorp. This team includes members from the University of Louisville, University of Texas at Austin, Via Therapeutics, VeriSIM Life, and Ossium Health. They will leverage high-throughput screening to identify biocompatible formulations that slow cellular metabolism and AI-assisted process optimization to develop a thin-film freeze-drying (TFFD) system that stabilizes cells at room temperature. 

DesiCorp will lead integration of the overall workflow by using a high-throughput screening platform to rapidly identify biocompatible formulations that enable cells to survive TFFD and resume function after rehydration. Meanwhile, UT Austin researchers will help optimize the TFFD critical process parameters and composition/material attributes, while also contributing expertise in aseptic processing and scaling up the technology. 

A third team is led by the University of California, Davis and includes scientists from Mayo Clinic, Case Western Reserve University, University of Georgia, and Sersense. The team will induce a low metabolic state in cells using light-responsive gels and microfluidic processing techniques to produce cells that are stable at room temperature. 

Recently, that team announced that it had been awarded up to $6 million, initially,  from ARPA-H to fund its project dubbed CYBORGEL. Their efforts will leverage research done in the laboratory of Cheemeng Tan, PhD, a professor of biomedical engineering at UC Davis. Previously, he and his collaborators formed water-rich polymer networks inside living cells to create cell-material hybrids. This process, called intracellular gelation, forms a gel inside the cell and is capable of halting cell division while preserving cellular function. Tan and his team dubbed this cellular product a “cyborg” since the gelation process combines living cells with synthetic materials. 

Through CYBORGEL, the collaborators will investigate whether this intracellular gelation process can be extended to reduce the cost and simplify the storage, transportation and delivery of cellular therapies. The researchers will also test whether CYBORGEL cells remain therapeutically useful after being returned to their original state. For instance, one study will test the effectiveness of reanimated CAR T cells for existing clinical trials on cancer immunotherapies. Another will test it on placental mesenchymal stem cells used to treat spina bifida, a medical intervention being developed by UC Davis researchers. 

As part of the initiative, the American Type Culture Collection (ATCC) has been tapped to serve as the IV&V partner. ATCC will provide working cell banks of government-selected cell types that will be used for demonstrations. They will also provide unbiased assessments of both the viability and function of the preserved products and the design features of the preservation systems.  

The first phase of the BoSS program kicked off in September and is expected to run for 15 months. Over the four-year multi-phase program, the teams’ approaches will be evaluated against increasingly stringent benchmarks for cell viability, production speed, and shelf-life stability. If successful, work under the BoSS program could enable lower costs for cell-based drugs, reduce the risk of therapeutic and pharmaceutical product losses, and enable domestic reserves for public health preparedness. 

The post ARPA-H’s BoSS Program Funds Three Teams Tackling Cold Chain Challenges for Cell Therapies appeared first on GEN - Genetic Engineering and Biotechnology News.