Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States.
Diabetes Center, University of California San Francisco, San Francisco, CA, United States.
Front Immunol. 2021 Nov 18;12:744763. doi: 10.3389/fimmu.2021.744763. eCollection 2021.
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 10 (range 56.9-16,179 x 10). 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.
我们报告了在 10 年期间（2011-2020 年）为 7 项不同的 1 期临床试验制造的 41 种自体多克隆调节性 T 细胞（PolyTreg）产品的制造结果。从制造批记录中收集了有关患者特征、制造参数和制造结果的数据，并将其输入到安全数据库中。总体而言，88%（36/41）的 PolyTreg 产品符合放行标准，83%（34/41）的产品成功输注给患者。在未输注的 7 个产品中，有 5 个未通过放行标准，另外 2 个未输注是因为患者由于临床状况的变化而失去资格。在 14 天的制造过程中，中位数的扩增倍数为 434.8 倍（范围为 29.8-2232），导致中位数的扩增后细胞数为 1841 x 10（范围为 56.9-16179 x 10）。扩增后细胞数量的主要相关因素是起始细胞数量，它与循环调节性 T 细胞计数呈正相关。其他参数，包括 PolyTreg 生产的日期、患者性别和年龄与 Treg 在产品制造过程中的扩增倍数没有显著相关性。总之，PolyTreg 的制造结果在各试验和生产日期之间是一致的。
