Clinical-grade tumor-reactive T cell manufacturing

The CliniMACS Prodigy® Tumor Reactive T (TRT) Cell Process offers a new, adaptable platform for scientists and clinicians working on tumor-infiltrating lymphocyte (TIL)  therapy, and can be tailored to the individual user’s desired indication and methodology. With our TRT process, it is possible to stimulate and isolate tumor-reactive T cells and then expand them in a closed, automated, GMP-compliant system in as little as two weeks.

Furthermore, specific tumor-reactive T cell populations can also be isolated with GMP-compliant cell sorting using the MACSQuant® Tyto® Cell Sorter. Discover how our technologies finally allow the realization of easy, safe, and effective personalized T cell medicines.

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CliniMACS Prodigy – Automated cell processing in a closed system

The CliniMACS Prodigy is a closed and automated platform that streamlines GMP-compliant cell manufacturing.

The CliniMACS Prodigy Platform covers the entire workflow for the manufacture of tumor-reactive T cells: T cell stimulation, selection (by CD137 activation marker), activation, and expansion. All cell processing steps are automated to ensure a highly reproducible and standardized manufacturing process and include an optional viral transduction. The TRT standard process offers a high level of flexibility:

  • Starting material for the process can be tumor digest, peripheral blood-derived leukapheresis product, or previously outgrown TILs.
  • Starting material can be stimulated and selected for CD137-expressing T cells, followed by an expansion and potential transduction of selected cells. However, stimulation and selection of the CD137-expressing TIL population is optional, allowing for cell expansion without enrichment if desired.
  • Alternatively, the user has the option to directly expand the total sample (e.g., tumor digest with low T cell infiltration) without prior enrichment.
Workflow overview of the TRT manufacturing process on the CliniMACS Prodigy.

Cell stimulation can be performed either manually, before connecting your starting material to the CliniMACS Prodigy, or automatically as the first step of the automated CliniMACS Prodigy TRT Process. If there is no need for activation at all, this step can be skipped.

Cells can be stimulated within the tumor digest by the tumor cells that are present in the mixture and/or by the addition of peptides of interest (e.g., MACS® GMP PepTivators® or predicted neo-antigens). Furthermore, cytokines such as MACS GMP Recombinant Human IL-7 and/or IL-15 can be added.

Cell separation on the CliniMACS Prodigy is a simple and easy method for magnetically isolating T cells with a high purity. Advantages of this completely automated method include:

  • Efficient separation of CD137+ cells (tumor-reactive) T cells
  • Removal of contaminating immune cells to enhance expansion efficiency and T cell transduction

MACS GMP CD3 pure and irradiated feeder cells are required for the activation and expansion of tumor-reactive T cells in the CliniMACS Prodigy TRT Process. Leukapheresis (allogeneic or autologous) or PBMCs can serve as source of feeder cells. These cells must be irradiated to prevent outgrowth during the expansion.

Viral transduction of the cells is possible via an optional transduction step. 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 TRT Process supports the use of both vectors.

Vectofusin-1 is compatible with both static and spiculation protocols. We also deliver tailored lentiviral solutions and advanced design and technology that meets global GMP requirements.

Cell expansion takes place in the cell cultivation chamber within the CliniMACS Prodigy Tubing Set. As part of the TRT process activity matrix, culture duration, medium supply, exchange rates, and further parameters are customizable.

Ideal cultivation and expansion of transduced T cells relies on the strong synergy of MACS GMP CD3 pure, 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

To sort the antigen-specific tumor-reactive T cells from TILs, we provide the revolutionary MACSQuant Tyto Cell Sorter. Our patented microchip-based technology opens new possibilities in basic research and medical applications. Using an integrated, optimized workflow, the MACSQuant Tyto Cell Sorter can sort defined antigen-specific tumor-reactive T cell populations, which can then be expanded afterwards using the previously described CliniMACS Prodigy TRT Process on the CliniMACS Prodigy.

Workflow overview of the TRT manufacturing process inlcuding the MACSQuant Tyto Cell Sorter.

Webinar
Harnessing the power of tumor-infiltrating lymphocytes for cell therapy

Explore the use of adoptive cell transfer therapy in the treatment of refractive metastatic melanoma! Dr Sandy Pelletier discusses her Montreal-based team’s way of overcoming the obstacles presented by using effector cells for immunotherapy.

Scientific poster
GMP-compliant flow cytometric cell sorting of antigen-specific T cells 

GMP-compliant flow cytometric cell sorting of antigen-specific T cells using MACS GMP CD8-APC and MACS GMP CD137-PE Fluorescent Antibodies on the MACSQuant Tyto Cell Sorter.

IPC/QC using MACSQuant Flow Cytometers

In-process control and quality control (IPC/QC) are required for consistent cell therapy manufacturing. Integrated sampling pouches on the CliniMACS Tubing Sets allow for controls to be collected at any time during the CliniMACS Prodigy TRT Process. With the MACSQuant Instruments and the MACS Flow Cytometry portfolio, including instruments, antibodies, optimized multicolor flow cytometry panels, flow kits, and protocols Miltenyi Biotec provides everything for a reliable and standardized IPC/QC of the clinical process. 

Every step in automated cell manufacturing on the CliniMACS Prodigy can be adapted to your specifications. In-process and quality control procedures via flow cytometry can also be tailored on a MACSQuant Analyzer using customized Express Modes for automated data analysis.

Related information

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