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.
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/neuCIR (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: Claudia M Kowolik; Max S Topp; Sergio Gonzalez; Timothy Pfeiffer; Simon Olivares; Nancy Gonzalez; David D Smith; Stephen J Forman; Michael C Jensen; Laurence J N Cooper Journal: Cancer Res Date: 2006-11-15 Impact factor: 12.701
Authors: Jinjuan Wang; Michael Jensen; Yukang Lin; Xingwei Sui; Eric Chen; Catherine G Lindgren; Brian Till; Andrew Raubitschek; Stephen J Forman; Xiaojun Qian; Scott James; Philip Greenberg; Stanley Riddell; Oliver W Press Journal: Hum Gene Ther Date: 2007-08 Impact factor: 5.695
Authors: Freddy Tita-Nwa; Gerhard Moldenhauer; Markus Herbst; Christian Kleist; Anthony D Ho; Martin Kornacker Journal: Cancer Immunol Immunother Date: 2007-05-09 Impact factor: 6.968
Authors: N Kato; J Tanaka; J Sugita; T Toubai; Y Miura; M Ibata; Y Syono; S Ota; T Kondo; M Asaka; M Imamura Journal: Leukemia Date: 2007-07-12 Impact factor: 11.528
Authors: Michael Merker; Verena Pfirrmann; Sarah Oelsner; Simone Fulda; Thomas Klingebiel; Winfried S Wels; Peter Bader; Eva Rettinger Journal: Oncotarget Date: 2017-08-02