NK cells are relatively easy to select from apheresis donations, but although typically approximately 5 × 108

cells can be obtained relatively pure, this may not represent a sufficient number for clinical efficacy [94]. Miller and colleagues therefore sought to expand transfused NK cells in vivo. Selected NK cells from HLA identical donors were transfused into 19 patients with high-risk AML after conditioning with low-dose total body irradiation or a combination of fludarabine and cyclophosphamide. The conditioning induced a rise of IL-15 and circulating NK cell numbers which showed enhanced cytotoxicity to leukaemia lasting more than 3 weeks. Five patients AZD6244 manufacturer achieved complete remission [95]. Other investigators have developed clinical-grade strategies to expand NK cells ex-vivo using B cell lines [96] or modified K562 cells [97]. Such techniques can yield 20–200-fold expansion of pure but activated NK cells over several weeks. Expanded cells are fully functional and kill leukaemia and tumour targets. Clinical trials using expanded NK cells have not yet been reported. Future developments may include combined

ex-vivo and in vivo expansion approaches. Allogeneic T cells Forskolin can be raised against mHag by peptide-pulsed DC or AML cells and are being used in treatment of relapsed leukaemia after stem cell transplantation. Outside the context of SCT, the occurrence in patients of CTL specific for AML supports the possibility

of using expanded autologous antigen-specific CTL to attack AML [3,86]. Adoptive transfer of leukaemia-specific T cells presents different challenges according to whether the transfused T cells are autologous or allogeneic in origin. Treatment with allogeneic T cells requires immunosuppression of the recipient to permit at least the short-term survival of the transfused cells. Two studies of allogeneic T cell transfer in non-transplant recipients have been reported [98,99]. Haploidentical donor lymphocyte transfusions were given to patients with diverse malignancies, including 13 patients with high-risk AML. Transfusion was followed by a cytokine storm without any Ergoloid sustained cellular engraftment, but there were tumour responses including five complete remissions in the AML patients [99]. Future developments will need to focus upon ways to achieve a short controlled engraftment sufficient to confer an anti-leukaemia effect perhaps by engineering T cells to escape immune attack, which may in turn require the co-insertion of a suicide gene as a safety precaution to prevent sustained persistence and expansion of the foreign T cell clone. Autologous T cell infusions can avoid the problems of alloreactivity of patient to donor or donor to patient. Here the problem is to generate sufficient numbers of T cells with powerful anti-leukaemia activity.