Anti-tumor effect of DNA-based vaccination and dSLIM immunomodulatory molecules in mice with Ph+ acute lymphoblastic leukaemia.

ABSTRACT

Since the prognosis of patients with Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) still remains poor, new relapse prevention strategies are needed. We evaluated the pre-immunization of mice with DNA-based vaccines subsequently challenged by the syngeneic Ph+ ALL cell line BM185. Ballistic transfer of minimalistic immunogenically defined gene expression (MIDGE) vectors encoding a BCR-ABLp185 fusion specific peptide or GM-CSF were used for in vivo transfection. DNA-based double stem-loop immunomodulators (dSLIM) were used as immune adjuvant. We present survival and functional data that DNA-based vaccination with BCR-ABLp185 fusion specific sequences, GM-CSF and dSLIM leads to an anti-tumor effect in mice challenged with a lethal Ph+ ALL dose and this effect depends on leukaemia-specific sequences.