T cells in the fight against leukaemia

A considerable proportion of haematological malignancies are treated with allogeneic haematopoietic stem cell transplantation (HSCT). The success of this therapy is hampered by adverse complications such as graft versus host disease (GvHD). This occurs when the donor T cells attack the patient’s tissues in addition to infections.

To minimise these transplant-related adverse effects, scientists on the EU-funded T-CONTROL (Donor T cells for immune control) project are proposing to use specific T cells to treat infection and tumour relapse as well as regulatory T cells to treat GvHD in transplanted patients. The project constitutes a continuation of the FP6 programme ALLOSTEM which had pioneered a cell selection strategy for isolating multi-virus specific T cell products. The so-called Streptamer technology is based on HLA molecules containing peptides of viruses, tumour-associated antigens or self-antigens.

This strategy has been further optimised into a standard operating procedure for the clinical isolation of T cells specific for various viruses (CMV, EBV, Adenovirus) or tumour antigens (proteinase 3, NY-ESO-1, WT-1, RHAMM and PRAME, MiHA HA-1). The virus-specific T cells will be selected from immune individuals while the anti-tumour T cells will be isolated from healthy individuals.

The consortium has also performed large-scale isolation of regulatory T cells and the method is currently being adapted for GMP clinical grade applications. This regulatory T cell product could also be used to prevent graft rejection as well as treat autoimmune diseases. Administration of these T cells to HSC-transplanted patients will take place during the second part of the project in clinical trials.

Overall, the study aims to improve the general outcome of HSCT and to develop strategies for reducing related complications. The proposed administration of virus-specific or leukaemia-specific T cells is expected to provide protective immunity against opportunistic infections while reducing the risks associated with allogeneic transplant procedures.