Genetic Engineering & Biotechnology News

JAN15 2018

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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22 | JANUARY 15, 2018 | | Genetic Engineering & Biotechnology News steps. I don't mean to make that sound negative—that really is a tremendous advance, and it's going well—but when we consider the future of cell therapy, we [will] need much more integrated, fully automated processing," he says. He notes that companies are already working to auto- mate the process from beginning to end. "The idea is going to be to introduce automation to increase process robustness and dramatically decrease operating costs." New Technology "Through newly developed and commercially available technology and equipment, cell therapy manufacturing— which incorporates our efforts here at Penn—is moving to- ward more automated, closed, scalable systems," Andrew Fesnak, M.D., director of clinical manufacturing develop- ment at the University of Pennsylvania, tells GEN. In his talk at the conference, Dr. Fesnak highlighted several newer technologies that have facilitated closed, scalable, automated approaches. Cell manufacturing stages include apheresis, which is a method for collecting blood cells from the body. "While pre- vious generations of apheresis-collection technology were closed and scalable," notes Dr. Fresnak, "they were also largely manual processes that required a lot of intervention." Now, he adds, with newer instruments, there is at least a pos- sibility that automation will be better incorporated. He explains that further downstream, several of the tradi- tional methods for separating cells of interest—also known as enrichment—are open and manual. Also, he points out, although the process is technically scalable—through the ad- dition of more test tubes—it's "not necessarily advisable" because risk of contamination increases, too. The newer enrichment processes, he says, incorporate closed, automated instruments and allow for increased scal- ability without increased risk. A few newer-age instruments that have been shown in the literature to work for enrich- ment include the Cell Saver ® 5+ (Haemonetics) and the Sepax ® system (Biosafe/GE Healthcare). 1,2 Another step Dr. Fesnak describes is expansion, during which cell population increases. He explains that the tradi- tional approach to expansion is manual and open, and that while this approach is technically scalable, space constraints may eventually become a problem. One study from 2016 detailed a procedure in which the time to generate CD19 chimeric antigen receptor (CAR) T cells was reduced from 10 to days to 6 days. 3 He notes there are several new products described recently in the literature, from simply de- signed products, such as G-Rex (Wilson Wolf) and Nunc ™ Cell Factory ™ systems (Thermo Fish- er Scientific), to more complex systems, such as CliniMACS Prodigy ® (Miltenyi Biotec) and Quantum ® Cell Expansion Sys- tem (Terumo BCT). 4–6 Xvivo GMP System Kevin Murray, vice president of global sales at BioSpherix Medical, gave a talk at the conference about the Xvivo GMP System, a closed system for processing cells (Figure 1). "It's basically a modular design that is constructed around the end user's protocol of their process. We essen- tially take everything they would normally do in the open lab and we integrate it and then close it," Mr. Murray says. The Xvivo GMP System is an alternative to a cleanroom and facilitates aseptic conditions for each cell process. "Cells are essentially in their happy space, so to speak, dur- ing the whole production process." He explains that in the past decade or so, features such as sensors, data-logging abilities, and software have been in- corporated into the Xvivo GMP System to make the system Cell Therapy Manufacturing: All Signs Point to Commercialization Continued from page 1 Figure 2. Clusters of cardiomyocytes differentiated from human pluripotent stem cells in suspension culture (10×). Image by Akiko Tsuchida at the University of Washington School of Medicine. Translational Medicine Feature One notable hurdle in cell therapy is being able to manufacture a consistent product on a large scale, which will increasingly become a concern as new cell therapies enter the clinic and subsequently come to market. Figure 1. Xvivo GMP System from BioSpherix Medical is an alternative to a traditional cleanroom. The system is closed, has advanced control features, and is made of modular sets of interconnecting clean benches, closed incubators, and closed hoods. Instruments such as microscopes and centrifuges can be integrated into the system. When someone gets a vaccine or is exposed to a new infectious agent, cells that recog- nize the invader but had never been called into action before—called naïve cells— respond by dividing and developing infection-fighting functions. This creates a pool of memory cells that are primed to provide protection later. A recent Nature study found that the pool of long-term memory T cells is maintained for years after vaccination through the develop- ment of several unique features. On the sur- face and through the actions of their genes, they look like naïve cells that have never been exposed to an infection, but their DNA contains a methylation pattern that identifies them as having been through battle as an infection-fighting cell. n Some Long-Term Memory T Cells Pretend to Be Naïve

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