1. ¹Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, USA
2. ²Department of Pediatrics, Keck School of Medicine, University of Southern California, USA
3. ³Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, USA

Correspondence: Dr Donald B Kohn, MD, Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 62, Los Angeles, CA 90027, USA. E-mail: dkohn@chla.usc.edu

Received 13 October 2004; Published online 6 May 2005.

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.