title: Gene therapy with GM-CSF, interleukin-4 and herpes simplex virus thymidine kinase shows strong antitumor effect on lung cancer.
abstract: BACKGROUND
  Inadequate release of tumor antigens (TA) and a defective antigen presentation by dendritic cells (DC) are the major mechanisms for how tumor cells can escape the host immune surveillance.
  
  
  METHODS
  Combined gene therapy of herpes simplex virus thymidine kinase (Tk), GM-CSF and IL-4 via adenoviral vector was tested to solve these problems. After establishing wild-type Lewis lung carcinoma (LLC), vaccinations with LLC transduced with Tk +/- GM-CSF +/- IL-4 were performed.
  
  
  RESULTS
  The LLC-Tk and LLC-Tk-IL-4 vaccination groups failed to suppress the wild-type LLC growth. However, the LLC-Tk-GM-CSF group showed a delayed wild-type tumor growth and LLC-Tk-GM-CSF-IL-4 markedly suppressed tumor growth and increased the survival rate of mice. Immunohistochemistry of the spleen showed a dense infiltration of DCs in the mice treated with LLC-Tk-GM-CSF-IL-4.
  
  
  CONCLUSIONS
  Combined gene therapy with Tk-GM-CSF-IL-4 was effective in inducing antitumor immunity by enhancing the DC functions.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Gene Therapy Laboratory of Clinical Research Institute, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, Korea.
authors.forename: Kyung-Ho
authors.initials: KH
authors.lastname: Park
authors.forename: Gyesu
authors.initials: G
authors.lastname: Kim
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Jang
authors.forename: Cheol Hyeon
authors.initials: CH
authors.lastname: Kim
authors.forename: Sung-Youn
authors.initials: SY
authors.lastname: Kwon
authors.forename: Chul-Gyu
authors.initials: CG
authors.lastname: Yoo
authors.forename: Young Whan
authors.initials: YW
authors.lastname: Kim
authors.forename: Hee Chung
authors.initials: HC
authors.lastname: Kwon
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Kim
authors.forename: Sung Koo
authors.initials: SK
authors.lastname: Han
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Shim
authors.forename: Choon-Taek
authors.initials: CT
authors.lastname: Lee
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000998:Antiviral Agents / Q000627:therapeutic use; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000628:therapy*; D003587:Cytomegalovirus / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D015774:Ganciclovir / Q000627:therapeutic use; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000502:physiology; D007157:Immunologic Surveillance; D007376:Interleukin-2 / Q000235:genetics / Q000502:physiology; D015847:Interleukin-4 / Q000235:genetics* / Q000502:physiology; D017921:Mastadenovirus / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000502:physiology; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics*; D013154:Spleen / Q000276:immunology; D013937:Thymidine Kinase / Q000235:genetics* / Q000502:physiology; D014161:Transduction, Genetic; D019139:Tumor Escape; D014611:Vaccination; D014764:Viral Proteins / Q000235:genetics* / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013937:Thymidine Kinase; D015774:Ganciclovir