Adoptive cellular immunotherapy: NK cells and bone marrow transplantation

Allogeneic bone marrow transplantation (BMT) has been increasingly used for the treatment of both neoplastic and non-neoplastic disorders. However, se rious obstacles currently limit the efficacy and thus more extensive use of BMT. These obstacles include: graft-versus-host disease (GVHD), relapse fr om the original tumor, and susceptibility of patients to opportunistic infe ctions due to the immunosuppressive effects of the conditioning regimen. Ov ercoming these obstacles is complicated by dual outcome of existing regimen s; attempts to reduce GVHD by depleting T cells from the graft, result in i ncreased rates of tumor relapse and failure of engraftment. On the other ha nd, efforts to increase graft-versus-tumor (GVT) effects of the transplant also promote GVHD. In this review, the use of natural killer (NK) cells to overcome some of these obstacles of allogeneic BMT is evaluated. Adoptive i mmunotherapy using NK cells after allogeneic BMT has several potential adva ntages. First, NK cells can promote hematopoiesis and therefore engraftment by production of hematopoietic growth factors. Second, NK cells have been shown to prevent the incidence and severity of GVHD. This has been shown to be at least partially due to TGF-TS, an immunosuppressive cytokine. Third, NK cells have been shown to augment numerous anti-tumor effects in animals after BMT suggesting a vital role of NK cells in mediating GVT effects. Fi nally, NK cells have been demonstrated to affect B cell recovery and functi on in mice. Therefore, understanding the mechanisms of beneficial effects o f NK cells after BMT may lead to significant increases in the efficacy of t his procedure.