Possibility of Adoptive Immunotherapy With Peripheral Blood-derived CD3−CD56+ and CD3+CD56+ Cells for Inducing Antihepatocellular Carcinoma and Antihepatitis C Virus Activity

  title={Possibility of Adoptive Immunotherapy With Peripheral Blood-derived CD3−CD56+ and CD3+CD56+ Cells for Inducing Antihepatocellular Carcinoma and Antihepatitis C Virus Activity},
  author={Marlen Doskali and Yuka Tanaka and Masahiro Ohira and Kohei Ishiyama and Hirotaka Tashiro and Kazuaki Chayama and Hideki Ohdan},
  journal={Journal of Immunotherapy},
We recently showed that interleukin (IL)-2-stimulated CD56+ cells derived from the liver exert vigorous cytotoxicity against hepatocellular carcinoma (HCC) by their binding to the tumor necrosis factor-related apoptosis-inducing ligand expressed on natural killer cells and the corresponding death receptors, and exhibit inhibitory effects on hepatitis C virus (HCV) replication by production of a high level of interferon-&ggr;. These findings prompted us to develop a technique to increase the… 
A different representation of natural T cells and natural killer cells between tumor-infiltrating and periphery lymphocytes in human hepatocellular carcinoma.
Different representation of natural T cells and NK cells in local tumor tissues and in the periphery blood of patients with HCC are described and a new type of FOXP3-expressing natural T cell spontaneously arising in the TILs of HCC is identified.
Increased numbers and functional activity of CD56+ T cells in healthy cytomegalovirus positive subjects
Using Class I HLA pentamers, it was found that CD56+ T cells from CMV+ subjects contained similar proportions of antigen‐specific CD8 + T cells to CD56− T cells in donors of several different HLA types, which strongly implicates CD56- T cells as being an important component of the cytotoxic T‐cell response to CMV in healthy carriers.
NK Cells Prevalence, Subsets and Function in Viral Hepatitis C
Innate immunity appears to play an important role in the pathogenesis of viral hepatitis C. Among various cell subsets of this immunity natural killer (NK) cells raised particular interest. These
Prevention of hepatitis C virus infection by adoptive allogeneic immunotherapy using suicide gene-modified lymphocytes: an in vitro proof-of-concept
It is demonstrated that allogeneic suicide gene-modified lymphocytes (SGMLs) could potently, dose- and time-dependently, inhibit viral replication and post-transplant immunosuppression may not interfere with this adoptive cell immunotherapy approach.
Natural killer cells inhibit pulmonary metastasis of hepatocellular carcinoma in nude mice
It is concluded that IL-2 may enhance the antitumor activity of the NK cells, and thereby inhibit the metastases of hepatocellular carcinoma in mice.
Generation of natural killer cells from hematopoietic stem cells in vitro for immunotherapy
The factors needed for NK cell differentiation in vitro are reviewed, which stem cell sources have been used, published protocols, challenges and future directions for Good Manufacturing Practice protocols are reviewed.
Quantitative Effect of Natural Killer–Cell Licensing on Hepatocellular Carcinoma Recurrence after Curative Hepatectomy
Tanimine and colleagues report that multiplicity of compound KIR-HLA genotypes in blood cells of patients with hepatocellular carcinoma (HCC) correlate with HCC recurrence, supporting therapeutic
Pilot study to determine the safety and feasibility of deceased donor liver natural killer cell infusion to liver transplant recipients with hepatocellular carcinoma
This is the first-in-human immunotherapy study using deceased donor liver-derived NK cells to prevent HCC recurrence after LT, and this treatment was well tolerated and resulted in no HCCRecurrent after LT.


A novel population of expanded human CD3+CD56+ cells derived from T cells with potent in vivo antitumor activity in mice with severe combined immunodeficiency.
A novel population of cytotoxic cells can be generated readily from T cells that have superior in vivo antitumor activity in SCID mice, as compared with LAK cells.
Two pathways of exocytosis of cytoplasmic granule contents and target cell killing by cytokine-induced CD3+ CD56+ killer cells.
The results indicate that two mechanisms of cytoplasmic granule release are operative in the CD3+ CD56+ killer cells; however, cytotoxicity proceeds through a cAMP-sensitive, CsA- and FK506-insensitive pathway triggered by yet-to-be-identified target cell surface molecules.
Difference in cytotoxicity against hepatocellular carcinoma between liver and periphery natural killer cells in humans
O adoptive transfer of IL‐2–stimulated NK cells extracted from donor liver graft perfusate could mount an anti‐tumor response without causing toxicity against 1‐haplotype identical recipient intact tissues, and present a concept to prevent recurrence of HCC after liver transplantation.
Inhibition of Natural Killer Cells through Engagement of CD81 by the Major Hepatitis C Virus Envelope Protein
It is reported that ligation of an HCV receptor (CD81) inhibits natural killer (NK) cells, implicate HCV-E2–mediated inhibition of NK cells as an efficient HCV evasion strategy targeting the early antiviral activities ofNK cells and allowing the virus to establish itself as a chronic infection.
Long-term growth of lymphokine-activated killer (LAK) cells: role of anti-CD3, beta-IL 1, interferon-gamma and -beta.
These approaches may enable the in vitro generation from individual donors of much greater numbers of LAK cells for adoptive immunotherapy than can now be obtained with the 3 to 5 day in vitro culture systems.
Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer.
It is suggested that haploidentical NK cells can persist and expand in vivo and may have a role in the treatment of selected malignancies used alone or as an adjunct to HCT.
Binding of the Hepatitis C Virus Envelope Protein E2 to CD81 Inhibits Natural Killer Cell Functions
It is shown that CD81 cross-linking via immobilized E2 or mAbs specific for CD81 inhibits not only non major histocompatibility complex–restricted cytotoxicity mediated byNK cells but also interferon (IFN)-γ production by NK cells after exposure to interleukin (IL)-2, IL-12,IL-15, or CD16 cross- linking.
TGF-beta 1 promotes in vitro development of dendritic cells from CD34+ hemopoietic progenitors.
The cytokine combination granulocyte-macrophage CSF plus TNF-alpha and stem cell factor (SCF) commonly used for the in vitro generation of DC in serum/plasma-supplemented medium is, in the absence of serum supplementation, very inefficient in inducing DC development.
Minimally Invasive Treatment Combined With Cytokine-induced Killer Cells Therapy Lower the Short-term Recurrence Rates of Hepatocellular Carcinomas
The data suggest that CIK cell transfusion is an effective treatment that can boost the immunologic function in HCC patients and plays an important role in reducing the recurrence rate of HCC.