title: Dendritic Cell Immunotherapy Combined with Cytokine-Induced Killer Cells Effectively Suppresses Established Hepatocellular Carcinomas in Mice.
abstract: BACKGROUND
  The response of hepatocellular carcinoma (HCC) to immunotherapy is often disappointing and new strategies are clearly needed. The aim of the present study was to investigate whether cytokine-induced killer (CIK) cells combined with a dendritic cell vaccination enhanced cytotoxicity against hepatocarcinoma tumor cells in an in vivo animal model.
  
  
  METHODS
  CIKs and DCs were prepared from C3H/HeJ mice by conventional methods, the dendritic cell (DC) pulsed with a MH134 cell lysate, DC or CIK alone were used as controls. Cell phenotypes were analyzed by flow cytometry, cytokine secretion levels were determined by enzyme-linked immunosorbent assay (ELISA), and cytotoxicity was assessed by means of an in vitro lactate dehydrogenase (LDH) release assay. A mouse hepatocarcinoma cell MH134-bearing mice model was established to test the in vivo anti-tumor efficacy of the system.
  
  
  RESULTS
  CIK cells combined with DC therapy resulted in significant inhibition of tumor growth compared with the control group, whereas the decrease in tumor growth in mice that had been treated with CIK or DC alone did not reach the level of statistical significance. The combination therapy led to a further increase in the population of cytotoxic T cells (CTLs) in vivo, compared to the CIK or DC alone therapy. In addition, the combination therapy significantly enhanced cytotoxic activity against MH134 cells.
  
  
  CONCLUSIONS
  Taken together, these results show that a DC + CIK vaccination is more effective than DC or CIK alone therapy for the treatment of hepatocarcinoma cancer.
authors.affiliation: a Pharos Vaccine Inc ., Seongnam , Gyeonggi-do , Republic of Korea.
authors.forename: Nam-Chul
authors.initials: NC
authors.lastname: Jung
authors.affiliation: b Department of Biotechnology , CHA University , Seongnam , Gyeonggi-do , Republic of Korea.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: b Department of Biotechnology , CHA University , Seongnam , Gyeonggi-do , Republic of Korea.
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: a Pharos Vaccine Inc ., Seongnam , Gyeonggi-do , Republic of Korea.
authors.forename: Sung-Uk
authors.initials: SU
authors.lastname: Hwang
authors.affiliation: c Department of Radiation Cancer Research , Korea Institute of Radiological and Medical Sciences , Seoul , Republic of Korea.
authors.forename: Jie-Young
authors.initials: JY
authors.lastname: Song
authors.affiliation: d Department of Animal Biotechnology , Konkuk University , Seoul , Republic of Korea.
authors.forename: Han Geuk
authors.initials: HG
authors.lastname: Seo
authors.affiliation: e Division of Rheumatology, Department of Internal Medicine , Bundang CHA Medical Center , Seongnam , Gyeonggi-do , Republic of Korea.
authors.forename: Jinjung
authors.initials: J
authors.lastname: Choi
authors.affiliation: e Division of Rheumatology, Department of Internal Medicine , Bundang CHA Medical Center , Seongnam , Gyeonggi-do , Republic of Korea.
authors.forename: Sang Youn
authors.initials: SY
authors.lastname: Jung
authors.affiliation: f Department of Food Science and Biotechnology , College of Animal Bioscience and Technology, Konkuk University , Seoul , Republic of Korea.
authors.forename: Sung Gu
authors.initials: SG
authors.lastname: Han
authors.affiliation: b Department of Biotechnology , CHA University , Seongnam , Gyeonggi-do , Republic of Korea.
authors.forename: Dae-Seog
authors.initials: DS
authors.lastname: Lim
mesh_terms: D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D055612:Cytokine-Induced Killer Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D004195:Disease Models, Animal; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D061251:Primary Cell Culture; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D016207:Cytokines; D007770:L-Lactate Dehydrogenase
keywords: Cytokine-induced killer cells; dendritic cells; hepatocellular carcinoma