Donor Cells For Immune Therapy For Patients With Leukaemia

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Cancer / Oncology;  Blood / Hematology
Article Date: 23 Oct 2008 - 4:00 PDT

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In the future, the bone marrow transfer to patients with leukaemia could be more secure. Experiments with mice have shown already that certain cells of the immune system (regulatory T cells or Tregs) can suppress the dangerous side effects resulting from the treatment. Such cells control aggressive immune cells and, thus, unwanted immune reactions by the graft can be avoided. However, to date, there were no adequate techniques available to securely isolate the regulatory T cells. Now, Dr. Markus Kleinewietfeld, Dr. Kirsten Falk, and Dr. Olaf Rötzschke of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany and their colleagues of the 'Fondazione Santa Lucia' in Rome, Italy have developed a simple method to specifically isolate these cells from human blood. (Blood, doi 10 1182/blood-2008-04-150524)*

According to the American Cancer Society, about 188,000 people world-wide developed leukaemia in 2007. Predominantly immature white blood cells can be found in their blood. These cells displace the healthy cells and, thus, suppress a normal haematopoiesis. Chemotherapy destroys the diseased cells of the patient which then often have to be replaced by a bone marrow graft.

"However," says Dr. Kleinewietfeld, "in 30 to 50 percent of the patients, the aggressive immune cells contaminating the bone marrow graft direct themselves against the recipient." This often lethal defence reaction is called 'Graft versus Host Disease' (GvHD). Yet, with the help of regulatory T cells from the blood of the donor, the rejection reaction might be suppressed.

"Until now, it was not possible to securely isolate regulatory T cells in their pure form," explains Dr. Kleinewietfeld. Since, in humans, the cell surface marker (CD25) used for the isolation before is also found on the aggressive immune cells, it was hardly possible to clearly separate the helpful Tregs from the dangerous cells.

With other markers (CD49d and CD127), the scientists now succeeded in separating the aggressive and dangerous immune cells from the helpful, regulatory cells. Thus, it is now possible to isolate regulatory T cells in high purity safely from human blood. Using these T cells, the researchers could already suppress a particular severe form of the 'Graft versus Host Disease' in mice. In a first clinical trial in Singapore, the MDC researchers now want to apply the regulatory cells in leukaemia patients who developed the severe immune reaction after a bone marrow donation.

"Singapore provides the infrastructure and financial commitment necessary for such trials," says Dr. Rötzschke, a former MDC researcher who now works at the 'Singapore Immunology Network' (SIgN) of the BIOPOLIS Campus. "Dependent on the outcome of this clinical test, regulatory T cells could possibly be used also for the treatment of autoimmune diseases, allergies and tissue rejections in the future," hopes Dr. Falk, head of the MDC research group.

* "CD49d provides access to 'untouched' human Foxp3+ Treg free of contaminating effector cells."
Markus Kleinewietfeld1, Mireille Starke1, Diletta Di Mitri2, Giovanna Borsellino2, Luca Battistini2, Olaf Rötzschke1,3, Kirsten Falk1
1 Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Str. 10, D-13125 Berlin, Germany

2 Laboratory of Neuroimmunology, Fondazione Santa Lucia, Via del Fosso di Fiorano 65, 00143 Rome, Italy

3 Singapore Immunology Network (SIgN), 8A Biomedical Grove, IMMUNOS, Singapore 138648, Singapore

Source
Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch