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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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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DOI: https://doi.org/10.1038/sj.cgt.7700839