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Establishing a master cell bank requires compliance with the federal regulations. These regulations work to ensure the quality, safety, and efficacy of the finished product. Importantly, the stringency of federal regulations for clinical trials tend to be based upon the risk and stage of clinical trial design, with the most stringent regulations being applied to products going for licensure. The content of this chapter is intended as a guide for approaching cell banks—particularly for early phase clinical studies—and should be helpful in designing manufacturing strategies. This chapter will provide an overview of key regulations and standards to consider during the initial validation phases of developing a bank, and then will cover the requirements of establishing cell banks and the testing required. Options for expanding mesenchymal stromal cells (MSCs) in bioreactors and flasks are also outlined as potential ways to create a master cell bank and what to consider with each method.

Background Cellular therapy offers an innovative, personalized alternative to traditional therapeutics aimed to treat cancer and viral infections. Often offered in experimental clinical trials, in 2016 a New York Times article argued that immunotherapy is reserved primarily for white patients due to barriers to access. Two prominent immunotherapy trials cited in the article reported 92% and 88% enrollment of white patients, while minority patients represented 9% and 10% of enrollment, respectively. Purpose To examine the races, ethnicity, and gender of patients enrolled in clinical cell therapy trials at Children's National, Washington DC to determine if the enrollment is representative of the current US population. Methods Demographic data was analyzed from databases obtained from IRB-approved cell therapy clinical trials initiated at our Institution. Results/Conclusions Of the patients (between ages of 1 and 64) enrolled into cell therapy clinical trials, 56% identified racially as white (n=95), while 20% identified as black (n=33), 9% as Asian (n=9), 19% as "other" (n=20), and 3% as "unknown" (n=5). Among the patients who reported race, 18% identified ethnically as Hispanic (n=31). By sex, 50% were male (n=85) and 50% were female (n=84). In the 2015 US census, 77% of participants identified racially as white, 13.3% as black, and 5.6% as Asian. As per the census, 17% of those surveyed identified ethnically as Hispanic. This stands in contrast to 2 published adult centered cell therapy studies mentioned in the New York Times in which 92% and 88% of patients were identified as white and minorities only constituted

Background: Adoptive immunotherapy using virus-specific cytotoxic T-lymphocyte (VST) products has been successful in restoring antiviral immunity after hematopoietic stem cell transplantation (HSCT). VST may be produced from a stem cell donor in 10-14 days using current rapid protocols, or banked, partially-HLA matched VST may be used as an “off the shelf” treatment. Objective: To evaluate the clinical efficacy of HSCT donor-derived VST and third-party VST for prevention or treatment of CMV, EBV, and adenovirus following HSCT. Design/Methods: VST were cultured from HSCT or third-party donors using a GMP-compliant rapid-manufacture protocol. VST were tested for specificity and non-alloreactivity via IFN-γ ELISpot and cytotoxicity assays. Patients were monitored for 45 days following infusion for toxicity and for up to 22 months for immune reconstitution. Results: Nineteen patients received VST on existing protocols, of which 15 products were derived from HSCT donors, and 6 were from partially matched, third-party donors. Sixteen patients were treated for CMV (N=11), EBV (N=5), and/or adenovirus infections(n=3), of which fourteen (88%) had partial or complete antiviral responses. Immune reconstitution against targeted viruses was seen using IFN-g ELISpot at a median time of 28 days following infusion. Three patients developed grade I-II GVHD within 45 days of VST infusion, all of which was treatment responsive. Sixteen of the 19 patients remain alive and free of active viral infection up to 22 months post-VST infusion. Conclusions: VST are effective for the restoration of antiviral following HSCT. Expansion of targeted viruses may further extend the utility of this therapy.

Human computation is an effective way to channel human effort spent playing games to solving computational problems that are easy for humans but difficult for computers to automate. We propose Thumbs-Up, a new game for human computation with the purpose of playing to rank search result. Our experience from users shows that Thumbs-Up is not only fun to play, but produces more relevant rankings than both a major search engine and optimal rank aggregation using the well-known Kemeny rule.