Abstract
The central hypothesis underlying specific anti-leukemia immunotherapy is that leukemic cells express antigenic determinants not expressed on their counterpart normal adult cells. We have developed a murine myeloid leukemia/tumor immunization model using the low-immunogenic WEHI3 leukemia in syngeneic mice. Mice preimmunized with irradiated, transduced IL-7-producing WEHI3 cells showed systemic protection and rejection of a lethal dose of intravenously (i.v.) injected parental WEHI3 cells (5 × 104) with 40% long-term survival. When vaccinated with a mixture of parental WEHI3 cells and IL-2-producing NIH-3T3 fibroblasts (5 × 105), 60% survival was observed. Vaccination with murine granulocyte–macrophage colony-stimulating factor (GM-CSF)-producing WEHI3 cells resulted in only 20% survival of i.v. challenged mice, and the additional combination of IL-2- and IL-7-producing vaccine did not reveal any additive or synergistic effects. Immunizing mice with a pre-established leukemia burden (injected with 5 × 104 WEHI3 cells, i.v., 3 days prior to immunization) did not cure or result in a prolongation of survival, indicating that improved methods of immunization are needed. Taken together, we have identified IL-7 and IL-2 as effective cytokines in our leukemia/vaccination model with only marginal activity by GM-CSF.
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de Vos, S., Kohn, D., Cho, S. et al. Immunotherapy against murine leukemia. Leukemia 12, 401–405 (1998). https://doi.org/10.1038/sj.leu.2400940
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DOI: https://doi.org/10.1038/sj.leu.2400940