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Targeted cytotoxic effect of anti-JL1 immunotoxin against a human leukemic cell line and its clinical implications

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Abstract

We have previously reported the identification of a unique thymocyte-specific surface molecule, JL1, which was detected using the monoclonal antibody (mAb), anti-JL1. Interestingly, JL1 was shown to be expressed in most leukemias, irrespective of their immunophenotype, and subpopulations of normal bone marrow (BM) mononuclear cells (MNCs). Here we investigated the potential usefulness of the anti-JL1 mAb as a therapeutic tool for leukemia. We demonstrated that the proliferation of cultured human leukemia cells was dramatically inhibited in vitro by anti-JL1 mAb conjugated with the polypeptide toxin, gelonin, but not by gelonin alone. We then systematically investigated the reactivity of the anti-JL1 mAb against normal human tissues to evaluate possible side effects along with various hematopoietic and nonhematopoietic tumor cell lines. All of 33 types of normal tissues except thymus and subpopulation of BM MNCs were clearly devoid of JL1 expression. Among tumor cell lines, all the nonhematopoietic cell lines tested were negative for JL1 expression, while some hematopoietic cell lines contained JL1 antigen. Collectively, the results showed the cytotoxic effects of anti-JL1-based immunotoxin against JL1-positive leukemic cells, sparing most normal tissues other than thymocytes and some BM MNCs. Therefore, we strongly suggest that gelonin-conjugated anti-JL1 mAb immunotoxin could be developed as a potential immunotherapeutic agent in the treatment of various types of JL1-positive acute leukemias.

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Acknowledgements

This work was supported in part by a research grant (no. M1010400012401J00000551) from the National Research Laboratory Program of the Korea Ministry of Science and Technology and the 01' DiNonA R&D Project, Seoul, Korea. We are grateful to S.K. Chung (Keimyung University Hospital, Taegu) for helpful technical support.

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Authors and Affiliations

  1. Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, 110-799, Seoul, Korea

    Young Kee Shin, Yoon La Choi, Eun Young Choi, Myeong-Cherl Kook & Seong Hoe Park

  2. Department of Pathology, Ilsan Paik Hospital, Inje University College of Medicine, Ilsan, Korea

    Min Kyung Kim

  3. Department of Biochemistry and Molecular Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

    Junho Chung

  4. National Cancer Center, Goyang, Korea

    Junho Chung

  5. Genetic Resources Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea

    Yang-Kyu Choi

  6. Department of Pediatrics, Keimyung University College of Medicine, Taegu, Korea

    Heung Sik Kim

  7. Department of Pathology, Chungbuk National University College of Medicine, Chungju, Korea

    Hyung Geun Song

  8. DiNonA Inc., Seoul, Korea

    Young Kee Shin

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  1. Young Kee Shin
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  2. Yoon La Choi
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  7. Yang-Kyu Choi
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  8. Heung Sik Kim
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  9. Hyung Geun Song
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  10. Seong Hoe Park
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Correspondence to Seong Hoe Park.

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Y.K.S. and Y.L.C. contributed equally to this work.

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Shin, Y.K., Choi, Y.L., Choi, E.Y. et al. Targeted cytotoxic effect of anti-JL1 immunotoxin against a human leukemic cell line and its clinical implications. Cancer Immunol Immunother 52, 506–512 (2003). https://doi.org/10.1007/s00262-003-0374-y

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  • DOI: https://doi.org/10.1007/s00262-003-0374-y

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