15353-j-veluchamy

1 General introduction and Scope of this Thesis | 13 cells from transplanted grafts, is a major concern in the field of allogeneic HSCT. Under these circumstances, it is difficult to reliably study the safety of allogeneic NK cell infusions. The timing of NK cell infusion, NK cell dosage and NK cell promoting conditioning regimens are critical factors that need to be more extensively studied to assess the safety and efficacy of allogeneic NK cell infusions. Adoptive NK cell therapy in a non-transplant setting To gain a better understanding of the safety and efficacy of allogeneic NK cell transfer, investigators started to study NK cells in a non-transplant setting. Landmark clinical trials were performed by Miller et al 57 , Iliopoulou et al 60 , Rubnitz et al 61 , Bachanova et al 62 Curti et al 63 and Geller et al 40 , predominantly in hematological malignancies, but also in various solid tumors. These studies demonstrated the safety and in part the efficacy of allogeneic NK cell infusions in the absence of GvHD. A summary of allogeneic NK cell clinical trials in a non-transplant setting with published results 59 is presented in Table 2. Overall, analyzing the data from adoptive allogeneic NK cell therapy trials in a non-transplant setting, we conclude that such treatments are safe and well tolerated and efficacious in hematological malignancies, especially in AML, but as yet relatively ineffective in solid tumors. Trials using allogeneic NK cells alone yielded valuable information on the in vivo persistence, donor chimerism and anti-tumor potential in different indications. Furthermore, unlike combined approaches with HSCT, the absence of life threatening GvHD and major treatment related toxicities makes this method advantageous and provides an opportunity to further enhance the cytotoxic effects of allogeneic NK cells.