IMMUNOTHERAPY AGAINST MURINE LEUKEMIA

The central hypothesis underlying specific anti-leukemia immunotherapy is that leukemic cells express antigenic determinants not expressed o n their counterpart normal adult cells. We have developed a murine mye loid leukemia/tumor immunization model using the low-immunogenic WEHI3 leukemia in syngeneic mice. Mice preimmunized with irradiated, transd uced IL-7-producing WEHI3 cells showed systemic protection and rejecti on of a lethal dose of intravenously (i.v.) injected parental WEHI3 ce lls (5 x 10(4)) with 40% long-term survival. When vaccinated with a mi xture of parental WEHI3 cells and IL-9-producing NIH-3T3 fibroblasts ( 5 x 10(5)), 60% survival was observed. Vaccination with murine granulo cyte-macrophage colony-stimulating factor (GM-CSF)-producing WEHI3 cel ls resulted in only 20% survival of i.v. challenged mice, and the addi tional combination of IL-2- and IL-7-producing vaccine did not reveal any additive or synergistic effects. Immunizing mice with a pre-establ ished leukemia burden (injected with 5 x 10(4) WEHI3 cells, i.v., 3 da ys 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 cytokin es in our leukemia/vaccination model with only marginal activity by GM -CSF.