Process development and validation of expanded regulatory T cells for prospective applications: an example of manufacturing a personalized advanced therapy medicinal product

Journal of Translational Medicine

Gaetano La Manna¹  Matteo Cescon²  Roberto M. Lemoli³  Francesca Ulbar⁴  Mariele Viganò⁵  Sara Savelli⁵  Silvia Budelli⁵  Marta Giulia Cannone⁵  Elisa Groppelli⁵  Cristiana Lavazza⁵  Rosaria Giordano⁵  Elisa Montelatici⁵  Tiziana Montemurro⁵  Lorenza Lazzari⁵  Lucia Catani⁶ 

[1] Department of Experimental, Diagnostic and Specialty Medicine (DIMES)-Nephrology, Dialysis and Renal Transplant Unit, St. Orsola Hospital IRCCS, University of Bologna, Bologna, Italy;Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy;Department of General Surgery and Transplantation, University of Bologna, Bologna, Italy;Department of Internal Medicine (DiMI), Clinic of Hematology, University of Genoa, Genoa, Italy;IRCCS Ospedale Policlinico S. Martino, Genoa, Italy;Department of Medicine and Aging Sciences, University of Chieti-Pescara, Pescara, Italy;IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Dipartimento di Medicina Specialistica, Diagnostica E Sperimentale, Università di Bologna, Bologna, Italy;Department of Transfusion Medicine and Hematology, Laboratory of Regenerative Medicine, Cell Factory, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy;IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Dipartimento di Medicina Specialistica, Diagnostica E Sperimentale, Università di Bologna, Bologna, Italy;

关键词: ATMP;    GMP process development;    Process validation;   

DOI  :  10.1186/s12967-021-03200-x

来源: Springer

【 摘 要 】

BackgroundA growing number of clinical trials have shown that regulatory T (Treg) cell transfer may have a favorable effect on the maintenance of self-tolerance and immune homeostasis in different conditions such as graft-versus-host disease (GvHD), solid organ transplantation, type 1 diabetes, and others. In this context, the availability of a robust manufacturing protocol that is able to produce a sufficient number of functional Treg cells represents a fundamental prerequisite for the success of a cell therapy clinical protocol. However, extended workflow guidelines for nonprofit manufacturers are currently lacking. Despite the fact that different successful manufacturing procedures and cell products with excellent safety profiles have been reported from early clinical trials, the selection and expansion protocols for Treg cells vary a lot. The objective of this study was to validate a Good Manufacturing Practice (GMP)-compliant protocol for the production of Treg cells that approaches the whole process with a risk-management methodology, from process design to completion of final product development. High emphasis was given to the description of the quality control (QC) methodologies used for the in-process and release tests (sterility, endotoxin test, mycoplasma, and immunophenotype).ResultsThe GMP-compliant protocol defined in this work allows at least 4.11 × 109 Treg cells to be obtained with an average purity of 95.75 ± 4.38% and can be used in different clinical settings to exploit Treg cell immunomodulatory function.ConclusionsThese results could be of great use for facilities implementing GMP-compliant cell therapy protocols of these cells for different conditions aimed at restoring the Treg cell number and function, which may slow the progression of certain diseases.

【 授权许可】

CC BY