title: Safety analysis of ex vivo-expanded NK and NK-like T cells administered to cancer patients: a phase I clinical study.
abstract: The chimeric state after allogeneic hematopoietic stem cell transplantation provides a platform for adoptive immunotherapy using donor-derived immune cells. The major risk with donor lymphocyte infusions (DLIs) is the development of graft-versus-host disease (GvHD). Development of new DLI products with antitumor reactivity and reduced GvHD risk represents a challenging task in cancer immunotherapy. Although natural killer (NK) and NK-like T cells are promising owing to their antitumor activity, their low concentrations in peripheral blood mononuclear cells reduces their utility in DLIs. We have recently developed a system that allows expansion of clinical-grade NK and NK-like T cells in large numbers. In this study, the safety of donor-derived long-term ex vivo-expanded human NK and NK-like T cells given as DLIs was investigated as immunotherapy for cancer in five patients following allogeneic stem cell infusion. Infusion of the cells was safe whether administered alone or with IL-2 subcutaneously. No signs of acute GvHD were observed. One patient with hepatocellular carcinoma showed markedly decreased serum alpha-fetoprotein levels following cell infusions. These findings suggest that the use of ex vivo-expanded NK and NK-like T cells is safe and appears an attractive approach for further clinical evaluation in cancer patients.
authors.affiliation: Karolinska University Hospital Huddinge F79, SE-14186 Stockholm, Sweden. lisbeth.barkholt@ki.se
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Barkholt
authors.forename: Evren
authors.initials: E
authors.lastname: Alici
authors.forename: Reka
authors.initials: R
authors.lastname: Conrad
authors.forename: Tolga
authors.initials: T
authors.lastname: Sutlu
authors.forename: Mari
authors.initials: M
authors.lastname: Gilljam
authors.forename: Birgitta
authors.initials: B
authors.lastname: Stellan
authors.forename: Birger
authors.initials: B
authors.lastname: Christensson
authors.forename: Hayrettin
authors.initials: H
authors.lastname: Guven
authors.forename: Niklas K
authors.initials: NK
authors.lastname: Björkström
authors.forename: Gunnar
authors.initials: G
authors.lastname: Söderdahl
authors.forename: Kerstin
authors.initials: K
authors.lastname: Cederlund
authors.forename: Eva
authors.initials: E
authors.lastname: Kimby
authors.forename: Johan
authors.initials: J
authors.lastname: Aschan
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
authors.forename: Hans-Gustaf
authors.initials: HG
authors.lastname: Ljunggren
authors.forename: M Sirac
authors.initials: MS
authors.lastname: Dilber
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000209:etiology* / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D047368:Tumor Burden / Q000276:immunology