Genetic Engineering & Biotechnology News

JAN15 2018

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Genetic Engineering & Biotechnology News | GENengnews.com | JANUARY 15, 2018 | 23 compliant with good manufacturing require- ments and best practices. A closed system such as the Xvivo GMP System has several advantages, one of which is having "superior contamination control," he asserts. Another is having better process con- trol, which leads to a more consistent product. The third advantage is lower operating costs. "This industry is going to have to move to closed, automated ways of manufacturing products if it's going to be cost-effective to make," he insists. Bridging Academia and Industry "Processes developed in academic labs have what people in the field call 'art,'" Benjamin Fryer, Ph.D., team leader of car- diomyocyte cell manufacturing at the Uni- versity of Washington School of Medicine, tells GEN. "You have a specific person in the lab who knows how to make the process work, and they're the one others turn to if they lack the art themselves. The protocols aren't often very specific, or if they're specific, you have to have done it and really understand it," he says. Dr. Fryer has been working at the Univer- sity of Washington on transforming the non- GMP process of making cardiomyocytes in an academic setting into a cGMP, clinical- grade manufacturing process. He gave a talk at the conference about the methods he and his team have been developing. They have created a five-stage clinical- grade process that spans from the starting cell, which is a pluripotent cell, to the final product cell, which is a cardiomyocyte (Figure 2). The five-stage process is specific to making cardio- myocytes, but, he says, the first three stages, and possibly the fourth, could be used for generally any cell therapy that begins with a pluripotent cell. Cardiomyocytes are under investigation for their ability to regenerate heart muscle after injury, such as a heart attack. In a study published in Nature, researchers in- jected human embryonic stem cell–derived cardiomyocytes into the damaged heart of a nonhuman primate, which the investiga- tors showed could remuscularize the heart. 7 As for the clinical-grade process he and his team are planning, Dr. Fryer comments, "We're really trying to take the risk out of the process, simplify it as much as pos- sible, and make it so robust and stable that it can be made by different people around the world in different labs. Ideally, people would always be able to find the compo- nents they need." Dr. Fryer explains that if one component, or reagent, in the supply chain suddenly be- comes unavailable, it could halt production and lead to a backorder. People could end up dying as a result, because they weren't able to get the therapy in time. Making a cell therapy is a "significant responsibility," he says. "When you think about that on the front end, you really want to plan for success." Other groups, such as City of Hope in California, are also developing clinical-grade manufacturing processes, he says. "Every- one's got a slightly different flavor to what we're doing, but there are many groups that are trying to do that same thing at the same time as us—whether it's to make heart cells or to make something else." CAR-T Cell Target Selection Using Innovative in Situ Hybridization Technology Chimeric antigen receptor T (CAR-T ) cells are promising treatments for hematologic and solid malignancies. CAR-T cells can recognize and eliminate neoplastic cells expressing specific protein antigens. However, the current generation of CAR-T cells cannot distinguish between neoplastic and normal cells that may also be expressing the same antigen, thus potentially resulting in "on-target/off-tumor" toxicity. In this GEN webinar, we will review the RNAscope® in situ hybridization (ISH) method and show applications of the technology in the CAR-T cell and immuno-oncology fields. We will demonstrate how RNAscope ISH can be utilized to identify novel CAR-T cell targets and subsequently qualify monoclonal antibodies directed against those targets for immunohistochemistry. We will show how ISH can be used to predict CAR-T cell target organ toxicity in preclinical mod- els. Finally, we will discuss optimal preparation of tissues, cell pellets, and cytospin slides for evaluation by ISH. A live Q&A session will follow the presentation, offering you a chance to pose questions to our expert panelists. Free Registration! www.GENengnews.com/RNAscope View It Now! On Demand DURATION: 60 minutes COST: Complimentary Speakers James B. Rottman, D.V.M, Ph.D., D.A.C.V.P. Senior Director of Translational Development Bluebird Bio Courtney Anderson, Ph.D. Group Leader, Applications Advanced Cell Diagnostics Produced with support from Webinars You Will Learn • How RNAscope ISH technology can streamline your target identification and selection workflows • The advantages of using ISH for immunotherapeutic target cell selection • How ISH evaluation of target expression in normal tissues can be used to predict CAR-T cell– induced toxicity • Optimal tissue, cell pellet, and cytospin slide preparation for RNAscope ISH Bioprocessing References 1. W.E. Janssen et al., "Large-Scale Ficoll Gradient Separations Using a Commercially Available, Effec- tively Closed, System," Cytotherapy 12(3), 418–424 (May 2010). 2. H. Singh et al., "Manufacture of Clinical-Grade CD19-Specific T Cells Stably Expressing Chimeric Antigen Receptor Using Sleeping Beauty System and Artificial Antigen Presenting Cells," PLOS One 8(5), e64138 (May 31, 2013). 3. T.L. Lu et al., "A Rapid Cell Expansion Process for Production of Engineered Autologous CAR-T Cell Therapies," Hum. Gene Ther. Methods 27(6), 209–218 (December 2016), doi: 10.1089/hgtb.2016.120. 4. P. Bajgain et al., "Optimizing the Production of Sus- pension Cells Using the G-Rex 'M' series," Mol. Ther. Methods Clin. Dev. 1, 14015 (May 14, 2014). 5. U. Mock et al., "Automated Manufacturing of Chimeric Antigen Receptor T Cells for Adoptive Im- munotherapy Using CliniMACS Prodigy," Cytotherapy 18(8), 1002–1011 (August 2016). 6. P.J. Hanley et al., "Efficient Manufacturing of Thera- peutic Mesenchymal Stromal Cells with the Use of the Quantum Cell Expansion System," Cytotherapy 16(8), 1048–1058 (August 2014). 7. J.J. Chong et al., "Human Embryonic Stem Cell- Derived Cardiomyocytes Regenerate Non-Human Primate Hearts," Nature 510(7504), 273–277 (June 12, 2014).

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