Feasibility of the adoptive transfusion of allogenic human leukocyte antigen-matched natural killer cells in patients with renal cell carcinoma

Patients with metastasized renal cell carcinoma have a poor prognosis with conventional therapies. The feasibility and safety of donating purified nat ural killer (NK) cells without additional cytokines were evaluated. In cont rast to all previous studies, the NK cells were derived from allogenic dono rs. The NK cell donors were HLA-C matched to enable NK cell inhibition via killer cell inhibitory receptors and HLA-C. This should obviate a graft-ver sus-host reaction against nonmalignant HLA-expressing tissues in the alloge nic constellation. The average number of cells applied per transfusion was 1.02 +/- 0.265 x 10(9). The purify of the NK cells was 85% to 95%, and most of the contaminating cells were monocytes. Twenty-six transfusions given t o 11 patients did not cause any minor or major adverse effects, with the ex ception of one episode of transient fever. One patient had an objective reg ression of his lung metastases that had been progressing continuously befor e. No cytotoxic HLA antibodies could be detected 3 weeks after the transfus ions. The observed tolerance to this therapeutic regimen suggests the need for further studies with increased doses of cytokine-activated NK cells.