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.