Transfer of Her-2/neu Specificity into Cytokine-Induced Killer (CIK) Cells with RNA Encoding Chimeric Immune Receptor (CIR)

• DOI: 10.1007/s10875-009-9308-6
• Publication Date: 2009-06-10T08:11:17Z
• Authors: Sung Hee Yoon; Jin Myung Lee; Sun-Je Woo; Min-Ji Park; Jung-Sun Park; Hye-Sung Kim; Mi-Young Park; Hyun-Jung Sohn; Tai-Gyu Kim
• Keywords: Cytotoxicity, Immunologic; 0301 basic medicine; Receptor, ErbB-2; Transplantation, Heterologous; Cell Culture Techniques; Mice, Nude; Neoplasms, Experimental; Adoptive Transfer; 3. Good health; Mice; 03 medical and health sciences; Cytokine-Induced Killer Cells; Electroporation; Treatment Outcome; Cell Line, Tumor; Animals; Humans; RNA; Cells, Cultured; Single-Chain Antibodies

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).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.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.