title: Kinetics and organ distribution of allogeneic natural killer lymphocytes transfused into patients suffering from renal cell carcinoma.
abstract: The transfusion of natural killer (NK) lymphocytes into patients suffering from malignant diseases is an approach of current interest in the field of immunotherapy. Little is known about the organ distribution, survival, and clearance of donor immune effector cells in cellular therapy, and no reports exist on these important parameters considering NK cells in particular or any other type of allogeneic lymphocytes in humans. In the context of a clinical Phase I/II study we examined the distribution of transfused allogeneic NK cells in patients suffering from renal cell carcinoma. The NK cells were ex vivo cultivated and activated before transfusion. To assess the circulation of the transfused cells in the peripheral blood, we used a nested PCR technique to detect HLA DRB1 alleles of the NK cell donors. Post-transfusion, all patients showed evidence of circulating donor cells for up to 3 days. After 7 days, all donor cells were cleared from the blood to undetectable levels. To assess organ distribution, (111)In-labeled NK cells were injected and monitored by whole-body scintiscans. A distribution to the whole body, with preference for liver, spleen, and bone marrow, was observed after a short initial uptake in the lungs. No activity was observed in lymphatic nodes. A total of 2/4 evaluable metastases showed a clear accumulation of transfused NK cells. The half-life corrected activity in all body compartments remained almost constant over the 6-day observation period in concordance with the absence of any excretion of radioactivity. This may indicate an extended survival of the transfused cells, despite their foreign nature, in the host organism.
authors.affiliation: Institute of Immunology and Transfusion Medicine, University of Lübeck School of Medicine, 23538 Lübeck, Germany.
authors.forename: J-M
authors.initials: JM
authors.lastname: Brand
authors.forename: B
authors.initials: B
authors.lastname: Meller
authors.forename: K
authors.initials: K
authors.lastname: Von Hof
authors.forename: J
authors.initials: J
authors.lastname: Luhm
authors.forename: M
authors.initials: M
authors.lastname: Bähre
authors.forename: H
authors.initials: H
authors.lastname: Kirchner
authors.forename: C
authors.initials: C
authors.lastname: Frohn
mesh_terms: D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005805:Genes, MHC Class I; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism / Q000637:transplantation; D016131:Lymphocyte Subsets / Q000378:metabolism / Q000637:transplantation; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction; D014018:Tissue Distribution; D014184:Transplantation, Homologous
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains