Transfer of Her-2/neu specificity into cytokine-induced killer (CIK) cells with RNA encoding chimeric immune receptor (CIR).
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.
Yoon
Sung Hee
SH
Department of Microbiology and Immunology, College of Medicine, Catholic University of Korea, Seoul, South Korea.
Lee
Jin Myung
JM
Woo
Sun-Je
SJ
Park
Min-Ji
MJ
Park
Jung-Sun
JS
Kim
Hye-Sung
HS
Park
Mi-Young
MY
Sohn
Hyun-Jung
HJ
Kim
Tai-Gyu
TG
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
D012313:RNA; D018719:Erb-b2 Receptor Tyrosine Kinases; D057127:Single-Chain Antibodies; C508053:ERBB2 protein, human