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=Volume 12 - 2021

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). Other parameters, including date of PolyTreg production, patient sex, and patient age did not significantly correlate with fold expansion of Treg during product manufacturing. The main correlate of post-expansion cell number was starting cell number, which positively correlates with absolute circulating Treg cell count. In conclusion, PolyTreg manufacturing outcomes are consistent across trials and dates of production.