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12 | Chapter 1 life-threatening complications which arise due to GvHD have completely overshadowed the beneficial effects of alloreactive NK and T cells, fueling efforts to use T cell depleted grafts 44 . Further, this led to the development of NK cell-based therapies coupled with T cell depleted HSCs to enhance the graft versus tumor effect (GvT) without causing GvHD. Unlike autologous NK cells, allogeneic NK cells are not restricted by the patient’s tumor’s HLA expression, which is an added advantage to mount an improved anti-tumor effect 45,46 . Current translational efforts that are explored as anti-cancer therapies include adoptive transfer of ex vivo activated and/or expanded allogeneic NK cells, either alone or in combination with HSCT. Sources of allogeneic NK cells used in the clinic Commonly used allogeneic NK cells are apheresis products collected from haploidentical and unrelated donor PBMC 47 . Another source is umbilical cord blood (UCB), from which NK cells are generated from CD34+ progenitor cells that undergo expansion and differentiation using cytokines and growth factors and thereby mature into cytolytic NK cells 48 . Apart from PBMC and UCB, allogeneic NK cells have also been obtained from the clonal cell line NK-92, derived from immortalized lymphoma NK cells 49,50 . Allogeneic NK cell therapy in a transplant setting Autologous or allogeneic HSCT serves as a curative regimen by reconstituting the immune system in hematological malignancies. At an earlier stage post HSCT, NK and T cells developing from the graft are immature and less in number with reduced functionality. Under those circumstances, the infusion of purified allogeneic NK cells was explored as a viable option to target minimal residual disease (MRD) and so prevent graft failure and relapse. Grafts for allogeneic HSCT and allogeneic NK cell treatments were obtained from HLAmatched/mismatched and related/unrelated donors 45,46 . Earlier clinical trials performed by Passweg et al (2004) 51 , Koehl et al (2005) 52 , Shi et al (2008) 53 , Yoon et al (2010) 54 , Rizzieri et al (2010) 55 and Brehm et al (2011) 56 have shown that NK cells can be safely administered prior to or post-HSCT in patients with different types of hematological diseases. Immune suppression is a pre-requisite for most of the allogeneic HSCT and NK cell infusions. A non-myeloablative conditioning regimen usually consisting of cyclophosphamide (Cy) and fludarabine (Flu) was found to facilitate NK cell persistence and expansion in vivo 57 . High doses of Cy/Flu caused pancytopenia and resulted in high plasma IL-15 levels which also correlated with the detection of adoptively transferred NK cells up to 14 days after infusion, thus suggesting that excess IL-15 was probably utilized by the NK cells to proliferate and persist longer in vivo 58 . A summary of clinical trials with allogeneic NK cell infusions in a HSCT setting with published results 59 is summarized in Table 1. Taken together, it is evident from these studies, as well as from many others, that GvHD, which is mainly caused by T