Manufacturing of gene-engineered hematopoietic stem cells

The CliniMACS Prodigy® Hematopoietic Stem Cell Engineering (HSCE) process automates manufacturing of gene-engineered hematopoietic stem cells (HSCs) by viral transduction of CD34+ cells. Manufacturing takes place in sterile and single-use tubing sets connected to the CliniMACS Prodigy Instrument, providing a functionally closed system. Its robust performance reduces donor variations while the flexible software allows for easy conversion of manual processes.

Overview of the CliniMACS Prodigy® HSC Engineering workflow.
Overview of the CliniMACS Prodigy® HSC Engineering workflow.

Viral transduction of CD34+ cells is a promising approach for treating inherited disorders such as sickle cell disease, ß-thalassemia, or primary immunodeficiencies1-3. The CliniMACS Prodigy® HSC Engineering process allows for manufacturing of gene-engineered HSCs from human CD34+ cells.

Stepwise procedure to manufacture gene-engineered HSCs

The CliniMACS Prodigy Cell Manufacturing Platform automates the generation of gene-engineered HSCs by viral transduction in a functionally closed system. All steps are automated and manufacturing takes place in sterile, single-use tubing sets, ensuring highly reproducible and standardized manufacturing processes.

Video
Manufacturing of gene-engineered HSCs with the CliniMACS Prodigy®

The CliniMACS Prodigy HSC Engineering process automates the viral transduction of HSCs in a functionally closed system based on sterile and single-use tubing sets.

Webinar
Miltenyi University: Manufacturing of gene-engineered HSCs

The CliniMACS Prodigy HSC Engineering process automates the manufacturing of gene-engineered HSCs by viral transduction. This process will standardize and facilitate the clinical research of inherited disorders.

Setup of the CliniMACS Prodigy TS 520 for the CliniMACS Prodigy HSC Engineering process.
Setup of the CliniMACS Prodigy TS 520 for the CliniMACS Prodigy HSC Engineering process.

The CliniMACS Prodigy HSC Engineering process uses human CD34+ cells as cellular starting material. They can be easily enriched from mobilized leukapheresis with the CliniMACS Prodigy or the CliniMACS Plus Instrument. Enriched CD34+ cells are transferred to a cell bag, then connected to the CliniMACS Prodigy Tubing Set (TS) 520.

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CD34+ stem cell enrichment with the CliniMACS® System

The combination of the CliniMACS® CD34 Reagent, CliniMACS Tubing Sets, CliniMACS Prodigy® and CliniMACS Plus Instruments allow for an automated and GMP-compliant CD34+ HSC enrichment.

CD34+ cells are pre-cultivated in HSC-Brew GMP Medium supplemented with MACS® GMP Recombinant Human Cytokines (SCF, TPO, Flt3-Ligand, and IL-3). Our MACS GMP Products are manufactured and tested under a quality management system (ISO 13485) and are compliant with relevant GMP guidelines.  
After pre-cultivation, the CD34+ cells are transduced with lentiviral vector and when needed, can be repeated to increase transduction efficiency.

Express Modes of the MACSQuant® Instruments allow for fully automated and standardized flow cytometry processes
Express Modes of the MACSQuant® Instruments allow for fully automated and standardized flow cytometry processes.

After transduction, the final cell product containing gene-engineered HSCs is washed twice and harvested in a 100 ml buffer of your choice. The gene-engineered HSCs are then ready for further processing, e.g., cryopreservation, or functional testing.
 

In-process and quality control to clinical flow cytometry

In-process and quality control (IPC/QC) are required for consistent cell manufacturing. Integrated sampling pouches on the CliniMACS Tubing Sets allow for controls to be collected at any time throughout the cell manufacturing process. Miltenyi Biotec provides complete solutions with its MACS Flow Cytometers and a wide portfolio of MACS IVD Antibodies that are produced to quality management system ISO 13485.

When using a MACSQuant® Instrument, Express Modes allow you to fully automate and standardize your flow cytometry process. The MACSQuant Instrument and the MACS Flow Cytometry portfolio are for research use only.

  1. de Dreuzy E. et al. (2016) Current and future alternative therapies for beta-thalassemia major. Biomed. J. 39: 24–38.
  2. Lebensburger, J. and Persons D. A. (2008) Progress toward safe and effective gene therapy for beta-thalassemia and sickle cell disease. Curr. Opin. Drug Discov. Devel. 11: 225–232.
  3. Papanikolaou E. and Anagnou N. P. (2010) Major challenges for gene therapy of thalassemia and sickle cell disease. Curr. Gene Ther. 10: 404–412.

Unless otherwise specifically indicated, Miltenyi Biotec products and services are for research use only and not for therapeutic or diagnostic use. For complete regulatory notes, please click here.

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