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Adoptive immunotherapy using human peripheral blood lymphocytes transferred with RNA encoding Her-2/neu-specific chimeric immune receptor in ovarian cancer xenograft model

Cancer Gene Therapy volume 16, pages 489–497 (2009)Cite this article

Abstract

The current gene transfer technology for single chain (scFv)-based chimeric immune receptor (CIR) has relied on retrovirus and lentivirus vectors which require a long time to obtain sufficient number of transduced cells and stably incorporate into genome. To ameliorate these limitations, we applied RNA electroporation to human peripheral blood lymphocytes (PBLs) activated with anti-CD3 antibody and interleukin-2 (IL-2) for 3 days and assessed that PBL transiently expressing anti-Her-2/neu CIR (CIR-PBL) containing signaling portion of CD28 and CD3ζ could elicit strong cytotoxicity in vitro and antitumor responses in vivo. The CIR-PBL expressed high level of CIR in CD4+, CD8+ and CD56+ cells. Her-2/neu-specific stimulation induced secretion of type-I cytokines including interferon-γ (IFN-γ), IL-8 and granulocyte-macrophage colony-stimulating factor, and IFN-γ secretion was mainly mediated by CD8+ T cells. CIR-PBL specifically killed SKOV3 cell line expressing Her-2/neu. Adoptive transfer of CIR-PBL in SKOV3 xenograft model led to significant inhibition of tumor growth compared with transfer of mock-transduced PBL and showed higher inhibition than those with Herceptin, humanized monoclonal antibody specific for Her-2/neu. These results provided evidence that electroporation of CIR RNA to human PBLs could be used for rapid generation and high number of therapeutic antigen-specific T cells for adoptive immunotherapy.

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Acknowledgements

We thank Dr Philip K Darcy for kindly providing retroviral vector encoding anti-Her-2/neu CIR. This study was supported by a grant of the Korea Health 21R&D Project, Ministry of Health & Welfare, Republic of Korea (0405-DB01-0104-0006).

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Authors and Affiliations

  1. Department of Microbiology and Immunology, College of Medicine, Catholic University of Korea, Seoul, Korea

    S H Yoon, J M Lee, H I Cho, E K Kim, H S Kim, M Y Park & T G Kim

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  1. S H Yoon
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Correspondence to T G Kim.

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Yoon, S., Lee, J., Cho, H. et al. Adoptive immunotherapy using human peripheral blood lymphocytes transferred with RNA encoding Her-2/neu-specific chimeric immune receptor in ovarian cancer xenograft model. Cancer Gene Ther 16, 489–497 (2009). https://doi.org/10.1038/cgt.2008.98

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