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Direct and indirect antitumor effects by human peripheral blood lymphocytes expressing both chimeric immune receptor and interleukin-2 in ovarian cancer xenograft model

Cancer Gene Therapy volume 17, pages 742–750 (2010)Cite this article

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Abstract

Human peripheral blood lymphocytes (PBLs) electroporated with RNA encoding anti-Her-2/neu-specific chimeric immune receptor (CIR) have been reported to elicit potent immune responses against SKOV3 tumors in a nude mouse model. However, CIR-electroporated PBL (CIR-PBL) did not proliferate, and the cell number rapidly decreased in the absence of exogenous interleukin-2 (IL-2). In this study, PBLs electroporated with both CIR and IL-2 RNA (CIR/IL-2-PBL) were studied to determine whether antitumor effects could be improved by adoptive immunotherapy. CIR and IL-2 were expressed in CIR/IL-2-PBL at levels similar to PBLs electroporated, with IL-2 RNA (IL-2-PBL) or CIR-PBL. Transfer of IL-2 RNA induced proliferation and prolonged survival of PBLs in vitro. In a xenograft model, both IL-2-PBL and CIR/IL-2-PBL showed significantly higher antitumor effects than CIR-PBL. The number of tumor-infiltrating natural killer (NK) cells was significantly increased in IL-2-PBL and CIR/IL-2-PBL. After NK cell depletion, IL-2-PBL showed significantly lower antitumor effects than CIR/IL-2-PBL. These results suggest that transfer of IL-2 RNA to CIR-PBL can promote NK cell infiltration of tumors and prolong survival of infused PBLs in vivo. RNA electroporated PBLs may represent efficient tools for delivery of functional molecules to tumors by multiple gene transfer.

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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 and Welfare, Republic of Korea (A040018).

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Authors and Affiliations

  1. Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    J M Lee, S H Yoon, H-S Kim & T-G Kim

  2. Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    S Y Kim, H-J Sohn & T-G Kim

  3. Department of Surgery, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    S-T Oh

  4. Department of Cellular Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    I-H Oh

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Correspondence to T-G Kim.

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Lee, J., Yoon, S., Kim, HS. et al. Direct and indirect antitumor effects by human peripheral blood lymphocytes expressing both chimeric immune receptor and interleukin-2 in ovarian cancer xenograft model. Cancer Gene Ther 17, 742–750 (2010). https://doi.org/10.1038/cgt.2010.30

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