AUTHOR=Balcerek Joanna , Shy Brian R. , Putnam Amy L. , Masiello Lisa M. , Lares Angela , Dekovic Florinna , Acevedo Luis , Lee Michael R. , Nguyen Vinh , Liu Weihong , Paruthiyil Sreenivasan , Xu Jingying , Leinbach Ashley S. , Bluestone Jeffrey A. , Tang Qizhi , Esensten Jonathan H. TITLE=Polyclonal Regulatory T Cell Manufacturing Under cGMP: A Decade of Experience JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.744763 DOI=10.3389/fimmu.2021.744763 ISSN=1664-3224 ABSTRACT=

We report on manufacturing outcomes for 41 autologous polyclonal regulatory T cell (PolyTreg) products for 7 different Phase 1 clinical trials over a 10-year period (2011-2020). Data on patient characteristics, manufacturing parameters, and manufacturing outcomes were collected from manufacturing batch records and entered into a secure database. Overall, 88% (36/41) of PolyTreg products met release criteria and 83% (34/41) of products were successfully infused into patients. Of the 7 not infused, 5 failed release criteria, and 2 were not infused because the patient became ineligible due to a change in clinical status. The median fold expansion over the 14-day manufacturing process was 434.8 -fold (range 29.8-2,232), resulting in a median post-expansion cell count of 1,841 x 106 (range 56.9-16,179 x 106). The main correlate of post-expansion cell number was starting cell number, which positively correlates with absolute circulating Treg cell count. Other parameters, including date of PolyTreg production, patient sex, and patient age did not significantly correlate with fold expansion of Treg during product manufacturing. In conclusion, PolyTreg manufacturing outcomes are consistent across trials and dates of production.