Recombinant murine interleukin-12 elicits potent antileukemic immune responses in a murine model of Philadelphia chromosome-positive acute lymphoblastic leukemia.
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.
Gruber
Tanja A
TA
Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles 90027, USA.
Skelton
Dianne C
DC
Kohn
Donald B
DB
D000818:Animals; D002460:Cell Line; D007155:Immunologic Factors / Q000235:genetics; D007156:Immunologic Memory / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D018664:Interleukin-12 / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D011994:Recombinant Proteins / Q000378:metabolism / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000379:methods
D007155:Immunologic Factors; D011994:Recombinant Proteins; D018664:Interleukin-12