Clinical-grade CAR T cell manufacturing via viral transduction
Automate and standardize your CAR T cell manufacturing process and safeguard your cells in a closed system setup. CliniMACS Prodigy® T cell Transduction (TCT) integrates all steps from cell isolation, activation, and transduction to expansion and harvest of your final cell product.
Chimeric antigen receptor (CAR) T cell therapy is undoubtedly leading a revolution in cancer therapy1. The recent successes of CAR T cell therapy in fighting hematologic malignancies have led to a tremendous increase of interest in the immunotherapeutic field2. The great potential of genetically modified T cells now even expands into the area of solid tumors and infectious diseases.3,4 Currently, the manufacturing process of CAR T cells consists of various complex procedures, is labor intensive, and represents one of the biggest challenges in this area. The CliniMACS Prodigy TCT process provides a unique all-in-one solution to these challenges. With the CliniMACS Prodigy Platform, it is possible to generate gene-modified T cells via viral transduction and in a standardized and automated process5. It is a breakthrough in cell manufacturing, and a leap to the next generation. Benefit from this widely used and well-established new technology, which is already being used in clinical settings6-9.
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The CliniMACS Prodigy T Cell Transduction Process
With the CliniMACS Prodigy T Cell Transduction (TCT) Process you can now generate CAR T cells in a simple and automated fashion. This easy-to-use and unique process will surely change the way you work.
The four easy steps to your final CAR T cell product
The CliniMACS Prodigy Platform enables the entire workflow for T cell transduction, from cell separation and activation , to genetic modification and cell expansion. All cell processing steps are automated, ensuring a highly reproducible and standardized manufacturing process.
Cell separation on the CliniMACS Prodigy is a simple and easy method to magnetically isolate T cells with a high purity. Advantages of this completely automated method include:
- Efficient separation of CD4+ and CD8+ cells without inducing activation
- Removal of contaminating immune cells to enhance T cell transduction efficiency
- No magnetic bead removal necessary
MACS® GMP T Cell TransAct™ is a colloidal polymeric nanomatrix conjugated to humanized, recombinant CD3 and CD28 agonists. It is a ready-to-use reagent that has been designed to activate and expand enriched T cell populations or resting human T cells from peripheral blood mononuclear cells (PBMCs). Thanks to its nanoscale structure the reagent can be sterile filtered and excess reagent can conveniently be removed by washing the TransAct activated cells.
MACS GMP T Cell TransAct is directly applicable for the use in automated culture systems, such as the CliniMACS Prodigy.
To achieve long-term gene expression through stable genomic insertion, two types of gene transduction tools are commonly used: gamma-retroviral vectors (RV) or lentiviral vectors (LV). The CliniMACS Prodigy TCT Process supports the use of both vectors.
The transduction enhancer Vectofusin®-1 is the perfect choice to boost your RV transduction efficiency. It is compatible with both static and spinoculation protocols.
Cell expansion takes place in the cell cultivation chamber, which is part of the CliniMACS Prodigy Tubing Set in order to maintain a closed system. As part of the TCT activity matrix, the cell culture duration as well as the medium supply and exchange are flexibly programmable.
Ideal cultivation and expansion of transduced T cells rely on the strong synergy of MACS GMP T Cell TransAct, TexMACS™ GMP Medium, and MACS GMP Cytokines.
TexMACS GMP Medium
- Specifically developed for T cell cultivation
- Serum- and xeno-component free
- Pharmaceutical-grade human serum albumin
- QC functionality test on every batch
MACS GMP Cytokines
- Lot-to-lot consistency and lot-specific certificates of analysis
- Designed according to the recommendations of <USP 1043> on ancillary materials
- Manufactured and tested under a certified ISO 13485 quality system
At the end of the CliniMACS Prodigy TCT, the cells are harvested in 100 mL buffer of your choice, e.g., CliniMACS® Formulation Solution. For the final filling of your cells for direct infusion or cryopreservation, the CliniMACS Formulation Unit can be used in combination with the CliniMACS Formulation Set. Our Customized Application Service is ready to develop your tailored process.
In-process and quality controls (IPC/QC) are required for consistent cell manufacturing. Integrated sampling pouches on the CliniMACS Tubing Sets allow for samples to be collected at any time during and at the end of the cell manufacturing process. Miltenyi Biotec provides complete solutions with its MACS Flow Cytometers, a wide portfolio of MACS IVD Antibodies, a time-saving and standardized staining procedure with StainExpress antibody cocktails, and automated flow cytometry analysis with Express Modes for clinical flow cytometry.
When using a MACSQuant® Instrument, Express Modes allow for fully automated and standardized flow cytometry processes. The MACSQuant Instrument and the MACS Flow Cytometry Portfolio are for research use only. MACS IVD Antibodies are produced according to the quality management system ISO 13485.
- Zhao, L. & Cao, Y.J. (2019) Engineered T cell therapy for cancer in the clinic. Front. Immunol. 10: 2250.
- Upadhaya, S. et al. (2020) Immuno-oncology drug development forges on despite COVID-19. Nature Reviews Drug Discovery 19: 751–752.
- Castellarin, M. et al. (2018) Driving cars to the clinic for solid tumors. Gene Ther. 25: 165–175.
- Seif, M. et al. (2019) CAR T cells beyond cancer: Hope for immunomodulatory therapy of infectious diseases. Front. Immunol. 10: 2711.
- Lock, D. & Mockel-Tenbrinck, N. et al. (2017) Automated manufacturing of potent CD20-directed chimeric antigen receptor T cells for clinical use. Hum. Gene Ther. 10: 914–925.
- Castella, M. et al. (2020) Point-of-care CAR T-cell production (ARI-0001) using a closed semi-automatic bioreactor: Experience from an academic phase I clinical trial. Front. Immunol. 11: 482.
- Jackson, Z. et al. (2020) Automated manufacture of autologous CD19 CAR-T cells for treatment of non-Hodgkin lymphoma. Front. Immunol. 7 (11): 1941.
- Maschan, M. et al. (2021) Multiple site place-of-care manufactured anti-CD19 CAR-T cells induce high remission rates in B-cell malignancy patients. Nat Commun. 12 (1): 7200.
- Shah, N.N. et al. (2020) Bispecific anti-CD20, anti-CD19 CAR T cells for relapsed B cell malignancies: a phase 1 dose escalation and expansion trial. Nat. Med. 26: 1569–1575.
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.
