Safety analysis of ex vivo-expanded NK and NK-like T cells administered to cancer patients: a phase I clinical study.
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.
Barkholt
Lisbeth
L
Karolinska University Hospital Huddinge F79, SE-14186 Stockholm, Sweden. lisbeth.barkholt@ki.se
Alici
Evren
E
Conrad
Reka
R
Sutlu
Tolga
T
Gilljam
Mari
M
Stellan
Birgitta
B
Christensson
Birger
B
Guven
Hayrettin
H
Björkström
Niklas K
NK
Söderdahl
Gunnar
G
Cederlund
Kerstin
K
Kimby
Eva
E
Aschan
Johan
J
Ringdén
Olle
O
Ljunggren
Hans-Gustaf
HG
Dilber
M Sirac
MS
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