TY - JOUR
T1 - Comparative Analysis of T-Cell Depletion Method for Clinical Immunotherapy—Anti–Hepatitis C Effects of Natural Killer Cells Via Interferon-γ Production
AU - Ohira, M.
AU - Nishida, S.
AU - Matsuura, T.
AU - Muraoka, I.
AU - Tryphonopoulos, P.
AU - Fan, J.
AU - Tekin, A.
AU - Selvaggi, G.
AU - Levi, D.
AU - Ruiz, P.
AU - Ricordi, C.
AU - Ohdan, H.
AU - Tzakis, A. G.
N1 - Funding Information:
Funding: Grants from the Florida Department of Health and the Bankhead-Coley Cancer Research Program (1BG-08).
Publisher Copyright:
© 2013 Elsevier Inc.
PY - 2013/6/1
Y1 - 2013/6/1
N2 - Liver transplantation (LT) is a life-saving treatment for liver cirrhosis patients with hepatocellular carcinoma (HCC). However, 10%-20% HCC recurrence rate after LT is due to the immunosuppression inducing tumor growth. We recently reported a novel immunotherapy with donor liver natural killer (NK) cells to prevent HCC and hepatitis C virus (HCV) recurrence after LT. In this cell processing procedure, Muromonab-CD3 (Orthoclone OKT3, an anti-CD3 antibody) was added to the culture medium to deplete CD3(+) T cells to prevent graft-versus-host disease. However, the manufacture of OKT3 was discontinued in 2010, when other treatments with similar efficacy and fewer side effects became available. In this study, we examined alternative reagents for T-cell depletion-MACS GMP CD3 pure (GMP CD3), antithymocyte globulin, and alemtuzumab-for NK cell immunotherapy in the allogeneic setting. We observed that GMP CD3 showed exactly the same effects on liver mononuclear cells as OKT3, including activation of NK cells and depletion of T cells. Interestingly, binding of T-cell depletion antibodies to NK cells led to an anti-HCV effect via interferon-γ production. These results with the use of in vitro culture systems suggested that antibodies which produce T-cell depletion affected NK cell function.
AB - Liver transplantation (LT) is a life-saving treatment for liver cirrhosis patients with hepatocellular carcinoma (HCC). However, 10%-20% HCC recurrence rate after LT is due to the immunosuppression inducing tumor growth. We recently reported a novel immunotherapy with donor liver natural killer (NK) cells to prevent HCC and hepatitis C virus (HCV) recurrence after LT. In this cell processing procedure, Muromonab-CD3 (Orthoclone OKT3, an anti-CD3 antibody) was added to the culture medium to deplete CD3(+) T cells to prevent graft-versus-host disease. However, the manufacture of OKT3 was discontinued in 2010, when other treatments with similar efficacy and fewer side effects became available. In this study, we examined alternative reagents for T-cell depletion-MACS GMP CD3 pure (GMP CD3), antithymocyte globulin, and alemtuzumab-for NK cell immunotherapy in the allogeneic setting. We observed that GMP CD3 showed exactly the same effects on liver mononuclear cells as OKT3, including activation of NK cells and depletion of T cells. Interestingly, binding of T-cell depletion antibodies to NK cells led to an anti-HCV effect via interferon-γ production. These results with the use of in vitro culture systems suggested that antibodies which produce T-cell depletion affected NK cell function.
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U2 - 10.1016/j.transproceed.2013.01.046
DO - 10.1016/j.transproceed.2013.01.046
M3 - Article
C2 - 23769105
AN - SCOPUS:84888306655
VL - 45
SP - 2045
EP - 2050
JO - Transplantation Proceedings
JF - Transplantation Proceedings
SN - 0041-1345
IS - 5
ER -