Gene Therapy with B7.1 and GM-CSF Vaccines in a Murine AML Model

Abstract

Characterization of B7.1 and GM-CSF vaccines on the induction of anti-tumor immunity in a murine AML model. Primary AML cells were retrovirally transduced with the murine costimulatory molecule B7.1, a natural ligand for the T-cell receptors CD28 and CTLA-4, or the cytokine GM-CSF. Mice were vaccinated with irradiated AML cells expressing B7.1 or GM-CSF before or after inoculation of wild type AML cells. Intravenous injection of irradiated B7.1 or GM-CSF expressing AML cells can provide long lasting systemic immunity against a subsequent challenge of wild type AML cells. Vaccination with irradiated B7.1 or GM-CSF expressing AML cells results in rejection of established leukemia when the vaccination occurs in the early stages of the disease. However, when the vaccines are administered >2 weeks after leukemic inoculation, only mice which receive the GM-CSF vaccine are cured of leukemia. Conclusions: These results suggest that tumor burden and vaccine efficiency are most likely to be the limiting factors in the curative potential of tumor vaccines. Novel approaches such as this experiment could provide improved therapeutic outcomes in patients with AML and other cancers.