Protection of mice against Philadelphia chromosome-positive acute lymphoblastic leukemia by cell-based vaccination using nonviral, minimalistic expression vectors and immunomodulatory oligonucleotides.

摘要: Purpose: Childhood Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) has a poor prognosis. Because cell burden is reduced but not eradicated by polychemotherapy, improved treatment strategies should enhance those immune mechanisms responsible for the maintenance of complete remission. The aim this study was to evaluate protection mice challenged with syngeneic Ph+ ALL line BM185 using genetically modified vaccines and immunomodulating oligonucleotides. Experimental Design: retroviral vectors are ineffective at transducing nondividing primary cells from human hematopoietic malignancies, we first evaluated nonviral techniques (electroporation ballistic transfer) minimalistic immunogenically defined gene expression generate B7.1 or granulocyte macrophage colony-stimulating factor (GM-CSF)-expressing cells. Subsequently, protective vaccination experiments these were performed in challenge mouse model. Results: Electroporation yielded high transfection rate (82.6% B7.1) moderate GM-CSF secretion/1 × 106 (228 pg), whereas transfer led lower (30.9%) secretion (614 pg). Secondly, immunized B7.1/interleukin 2- B7.1/GM-CSF-expressing vaccines. We observed better that received B7.1/GM-CSF vaccine compared receiving 2 vaccine. Protection additionally enhanced application double stem-loop oligonucleotide containing CpG motifs. Conclusion: Our data indicate immunization generated electroporation protected against murine challenge. Ultimately, approach may also lead clinical benefit patients ALL.