title: Transfer of Her-2/neu specificity into cytokine-induced killer (CIK) cells with RNA encoding chimeric immune receptor (CIR).
abstract: BACKGROUND
  Efficient RNA transfer to dendritic cell and T cells by electroporation have been successfully applied for immunotherapy. Herein, RNA electroporation was used to transfer antigen-specific receptor (scFv) gene to cytokine-induced killer cells (CIK).
  
  
  METHODS
  CIK was generated from peripheral blood mononuclear cells with anti-CD3 antibody, interleukin-2, and interferon (IFN)-gamma for 14 days and showed typical characteristics of CIK expressing both CD3+ and CD56+ markers and NKG2D+. CIK could lyse K562 cells, but not SKOV3 and MCF7/Her-2/neu.
  
  
  RESULTS
  After RNA encoding anti-Her-2/neu chimeric immune receptor (CIR) with signaling portion of CD28 and CD3zeta was electroporated to CIK, more than 95% of CIK expressed anti-Her-2/neu CIR (CIR-CIK). CIR-CIK was able to produce cytokines including IFN-gamma, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha, and show cytotoxicity specific to tumor cell lines expressing Her-2/neu, SKOV3, and MCF7/Her-2/neu. Adoptive transfer of CIR-CIK in SKOV3 xenograft nude mice model led to significant inhibition of tumor growth compared with transfer of mock-transduced CIK and showed higher inhibition than that of Herceptin, humanized monoclonal antibody specific for Her-2/neu. These results suggest that RNA transfer is the convenient and efficient strategy to introduce antigen-specificity into CIK and provide potential therapeutic value of CIR-CIK in the treatment of tumors.
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Catholic University of Korea, Seoul, South Korea.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Yoon
authors.forename: Jin Myung
authors.initials: JM
authors.lastname: Lee
authors.forename: Sun-Je
authors.initials: SJ
authors.lastname: Woo
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Park
authors.forename: Jung-Sun
authors.initials: JS
authors.lastname: Park
authors.forename: Hye-Sung
authors.initials: HS
authors.lastname: Kim
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Park
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Sohn
authors.forename: Tai-Gyu
authors.initials: TG
authors.lastname: Kim
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D055612:Cytokine-Induced Killer Cells / Q000276:immunology / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D018274:Electroporation; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000628:therapy*; D012313:RNA / Q000008:administration & dosage* / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D057127:Single-Chain Antibodies / Q000235:genetics*; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
chemical_list: D012313:RNA; D018719:Erb-b2 Receptor Tyrosine Kinases; D057127:Single-Chain Antibodies; C508053:ERBB2 protein, human