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HLA-restricted presentation of WT1 tumor antigen in B-lymphoblastoid cell lines established using a maxi-EBV system

Cancer Gene Therapy volume 19, pages 566–571 (2012)Cite this article

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Abstract

Lymphoblastoid cell lines (LCLs), which are established by in vitro infection of peripheral B-lymphocytes with Epstein–Barr virus (EBV), are effective antigen-presenting cells. However, the ability of LCLs to present transduced tumor antigens has not yet been evaluated in detail. We report a single-step strategy utilizing a recombinant EBV (maxi-EBV) to convert B-lymphocytes from any individuals into indefinitely growing LCLs expressing a transgene of interest. The strategy was successfully used to establish LCLs expressing Wilms’ tumor gene 1 (WT1) tumor antigen (WT1-LCLs), which is an attractive target for cancer immunotherapy. The established WT1-LCLs expressed more abundant WT1 protein than K562 leukemic cells, which are known to overexpress WT1. A WT1-specific cytotoxic T lymphocyte line efficiently lysed the WT1-LCL in a human leukocyte antigen-restricted manner, but poorly lysed control LCL not expressing WT1. These results indicate that the transduced WT1 antigen is processed and presented on the WT1-LCL. This experimental strategy can be applied to establish LCLs expressing other tumor antigens and will find a broad range of applications in the field of cancer immunotherapy.

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Acknowledgements

We thank K Semba (Waseda University) for providing us with WT1 complementary DNA plasmids. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (TK and TT), by a Grant-in-Aid for Scientific Research the Ministry of Health Labour and Welfare (TK and KK), by a grant of NOASTEC (Northern Advancement Center for Science and Technology) (TK), and by a grant from the Naito Foundation (TK).

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Authors and Affiliations

  1. Division of Virology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, Japan

    T Kanda & T Tsurumi

  2. Department of Bioregulatory Medicine, Ehime University, Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan

    T Ochi, H Fujiwara & M Yasukawa

  3. Center for Cell and Gene Therapy, Takara Bio, 3-4-1 Seta, Ohtsu, Shiga, Japan

    S Okamoto & J Mineno

  4. Disivion of Immunology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, Japan

    K Kuzushima

  5. Department of Cellular Oncology, Nagoya University Graduate School of Medicine, Nagoya, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan

    K Kuzushima

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  1. T Kanda
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  2. T Ochi
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  3. H Fujiwara
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  4. M Yasukawa
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Correspondence to T Kanda.

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Kanda, T., Ochi, T., Fujiwara, H. et al. HLA-restricted presentation of WT1 tumor antigen in B-lymphoblastoid cell lines established using a maxi-EBV system. Cancer Gene Ther 19, 566–571 (2012). https://doi.org/10.1038/cgt.2012.34

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