Cellular therapies

Project leaders: Daphne Thijssen PhD and Carlijn Voermans PhD

In the past years several research projects within Sanquin have led to the development of new cellular products. Some of these products are now ready to be introduced into the clinic. Due to European legislation, these cellular therapies are considered medicines which imply that they have to be manufactured under GMP conditions. Therefore Sanquin has created a new GMP facility within the Laboratory for Cell Therapy (LCT) to perform translational research and generate cell therapy products, so called advanced therapy medicinal products (ATMPs) for clinical trials. Our facility comprises four separate class B labs (one for ML-2 activities) and one class C lab. The LCT has received a GMP license (NL/H 14/1000028) in February 2014.

We currently produce mesenchymal stromal cells (MSCs) and tumor infiltrating lymphocytes (TIL) for clinical trials. Furthermore we work on the in vitro production of red blood cells within the ZonMw sponsored project “From iPS to transfusion ready erythrocytes”. Finally the LCT has developed a clinical grade closed culture system for production of dendritic cells.

Mesenchymal Stromal Cells

Mesenchymal stromal cells (MSCs) derived from the bone marrow can be used to treat acute graft-versus-host disease (GvHD). The LCT participates in a randomized phase III clinical trial conducted by HOVON (HOVON 113 trial) which started in January 2014. The trial design involves patients with acute GvHD grade 2-4, who are refractory on steroid treatment. The patients will be randomized to receive MSCs or placebo. The LCT will be one of the production centers for allogeneic bone marrow derived MSC products.

Tumor Infiltrating Lymphocytes

The LCT produces Tumor infiltrating lymphocytes (TIL) from resected metastases for administration to melanoma patients in an international randomized clinical trial on adoptive therapy. Patients will be treated in the Antoni van Leeuwenhoek hospital in Amsterdam under the supervision of prof J Haanen PhD.

Red Blood Cells

To guarantee future availability of red blood cells for all patients that require transfusions, the LCT participates in a research program (ZonMw/TAS) for in vitro culturing of red blood cells (cRBC). This is of particular interest for transfusion dependent patients with rare blood groups who have already made allo-antibodies. cRBC will be produced from buffy coats of healthy donors and tested for expansion and differentiation capabilities as well as neo antigen formation. Finally a trial will be conducted to study safety and stability of cRBC in healthy volunteers.

Dendritic Cells

Finally the LCT has developed a clinical grade closed culture system for production of DCs for clinical trials. Monocytes are efficiently matured towards DCs in Corning CellStack culture chambers in the presence of clinical grade MPLA and IFNgamma and show similar phenotypic characteristics as compared to DCs cultured in 6-wells plates or cell bags. Furthermore these MPLA and IFNgamma matured DCs are suitable for further manipulation such as RNA electroporation and subsequent application in cancer immunotherapies.

Laboratory for Cell Therapy

Key publications

Last edited on: 28 April 2014