Clinical-Scale Isolation of Interleukin-2-Stimulated Liver Natural Killer Cells for Treatment of Liver Transplantation with Hepatocellular Carcinoma

Autor: David Levi, Andreas G. Tzakis, Masahiro Ohira, Hideki Ohdan, Kohei Ishiyama, Gennaro Selvaggi, Seigo Nishida, Yuka Tanaka, Camillo Ricordi, Panagiotis Tryphonopoulos, Akin Tekin, Jang Moon
Rok vydání: 2012
Předmět:
Adult
Antigens
Differentiation
T-Lymphocyte
Graft Rejection
Male
Interleukin 2
Adoptive cell transfer
Carcinoma
Hepatocellular
Liver cytology
medicine.medical_treatment
Biomedical Engineering
lcsh:Medicine
Apoptosis
Biology
Liver transplantation
Natural killer cell
TNF-Related Apoptosis-Inducing Ligand
Young Adult
Interleukin 21
Antigens
CD
Secondary Prevention
medicine
Humans
Lectins
C-Type
Aged
Transplantation
Lymphokine-activated killer cell
Natural Cytotoxicity Triggering Receptor 2
Natural Cytotoxicity Triggering Receptor 1
Liver Neoplasms
lcsh:R
Cell Biology
Middle Aged
Tissue Donors
Liver Transplantation
Up-Regulation
Killer Cells
Natural
medicine.anatomical_structure
Liver
Immunology
Leukocytes
Mononuclear
Interleukin 12
Cancer research
Cytokines
Interleukin-2
Female
Immunotherapy
K562 Cells
medicine.drug
Zdroj: Cell Transplantation, Vol 21 (2012)
ISSN: 1555-3892
0963-6897
Popis: Tumor recurrence is the main limitation of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) and can be promoted by immunosuppressants. However, there is no prevention or treatment for HCC recurrence after LT. Here we describe a clinical-scale method for an adoptive immunotherapy approach that uses natural killer (NK) cells derived from deceased donor liver graft perfusate to prevent tumor recurrence after LT. Liver mononuclear cells (LMNCs) that were extracted from deceased donor liver graft perfusate contained a high percentage of NK cells (45.0 ± 4.0%) compared with peripheral blood mononuclear cells (PBMCs) (21.8 ± 5.2%) from the same donor. The CD69 activation marker and the natural cytotoxicity receptors, NKp44 and NKp46, were expressed at high levels in freshly isolated liver NK cells. Furthermore, interleukin-2 (IL-2)-stimulated NK cells showed greater upregulation of activation markers and the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is critical for NK cell-mediated antitumor cell death and increased production of interferon. Moreover, IL-2 stimulation induced LMNCs to exhibit a strong cytotoxicity against NK-susceptible K562 target cells compared with PBMCs ( p < 0.01). Finally, we also showed that the final product contained a very low T-cell contamination (0.02 ± 106 cells/kg−1), which reduces the risk of graft-versus-host disease (GVHD). Collectively, our results suggest that the adoptive transfer of IL-2-stimulated NK cells from deceased donor liver graft perfusate could be a promising treatment for LT patients with HCC.
Databáze: OpenAIRE
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