Challenges of cancer therapy with natural killer cells

Background aims. Natural killer (NK) cells from peripheral or cord blood-especially if they are obtained from a human leukocyte antigen-mismatched (allogeneic) donor-are increasingly being considered for treatment of malignant diseases and to prevent or treat relapse after stem cell transplant. However, in addition to proving their efficacy, there are some more logistical and technical issues that must be addressed before NK cell infusions will be fully accepted by the medical community. Methods. Issues include (i) the expansion of sufficient numbers of cells under conditions suitable, (ii) cryopreservation and (iii) optimization/standardization of shipping conditions if the cells are used at distant sites. Because the patient's own autologous cells usually are not fully functional because of inhibition by "self" major histocompatibility complex expression, better methods must be developed to target NK cells to tumor cells and overcome self-inhibition. Results. Tumor-directed NK-cell therapy can be best accomplished through genetic engineering of NK cells expressing receptors for tumor antigens or combination with monoclonal antibodies that preferentially kill tumors through antibody-dependent cellular cytotoxicity. If allogeneic NK cells are used, T-lymphocytes in the cell collections that can cause acute graft-versus-host disease in the recipient must be removed. Conclusions. In addition to showing efficacy in clinical trials, the production of NK cells for treatment must be cost-effective to be eligible for reimbursement by third-party players.