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Recombinant murine interleukin-12 elicits potent antileukemic immune responses in a murine model of philadelphia chromosome-positive acute lymphoblastic leukemia

Cancer Gene Therapy volume 12, pages 818–824 (2005)Cite this article

Abstract

Despite the success of chemotherapy regimens in the treatment of acute lymphoblastic leukemia (ALL), certain subsets of patients have a high rate of induction failure and subsequent relapse. One of these subsets of patients carry a translocation between chromosomes 9 and 22, the so called Philadelphia chromosome (Ph+). The result of this translocation is the fusion oncogene, Bcr-Abl, which is uniquely expressed in the leukemia clone, and as such has the potential to initiate antileukemic immune responses against the leukemia blasts. We utilized a murine model of Ph+ ALL to look at the ability of systemic interleukin 12 (IL-12) treatments to initiate antileukemic immune responses, and studied the mechanisms by which it does so. We found that IL-12 was able to eliminate pre-established leukemia, and that this protection was mediated by CD4, CD8, and NK cells in combination. While IL-12 was able to eliminate pre-established leukemia, it did not elicit immunologic memory. Consistent with previous work, vaccination with irradiated leukemia cells transduced with immunomodulator genes was able to establish long-term memory, and, when used with IL-12, was able to eradicate pre-existing disease and induce resistance to subsequent leukemia challenge. These studies demonstrate the feasibility of an immunotherapeutic approach towards the treatment of Ph+ ALL.

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Acknowledgements

We thank Lora Barsky for assistance in flow cytometry and Fred Dorey, PhD for statistical analysis. This work was supported in part by the Kenneth T and Eileen J Norris Foundation.

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Authors and Affiliations

  1. Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, USA

    Tanja A Gruber, Dianne C Skelton & Donald B Kohn

  2. Department of Pediatrics, Keck School of Medicine, University of Southern California, USA

    Donald B Kohn

  3. Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, USA

    Donald B Kohn

Authors
  1. Tanja A Gruber
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  2. Dianne C Skelton
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  3. Donald B Kohn
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Corresponding author

Correspondence to Donald B Kohn.

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Gruber, T., Skelton, D. & Kohn, D. Recombinant murine interleukin-12 elicits potent antileukemic immune responses in a murine model of philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer Gene Ther 12, 818–824 (2005). https://doi.org/10.1038/sj.cgt.7700839

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