Murine acute promyelocytic leukemia cells can be recognized and cleared in vivo by adaptive immune mechanisms

Abstract

BACKGROUND AND OBJECTIVES: In this study, we tested whether transgenic murine acute promyelocytic leukemia (APL) cells can be recognized and cleared by adaptive immune responses and/or vaccination strategies. DESIGN AND METHODS: Immunocompetent and SCID mice were examined for their ability to survive a challenge of APL cells. We also vaccinated immunocompetent mice with DNA vaccines encoding various portions of a bcr-1 PML-RARa fusion protein. RESULTS: In genetically compatible, immunocompetent animals, APL cells routinely engrafted and caused lethal leukemia; however, immunodeficient SCID mice required approximately 100-fold fewer APL cells to cause lethal disease. Massive doses of APL cells were efficiently eliminated in allogeneic recipients. Vaccination with a plasmid expressing a human PML-RARa cDNA conferred protection against leukemic cells in vivo; mice vaccinated with the human PML portion of the fusion gene demonstrated similar protection. Analysis of 10-mer peptides spanning the t(15;17) translocation-associated PML-RARa fusion breakpoint suggested that they were not involved in the generation of immune responses. INTERPRETATION AND CONCLUSIONS: These data show that tumor-specific immune clearance of APL cells does occur in mice. In this model system, the relevant immunogenic antigens may arise from the xenogenic PML portion of human PML-RARa, and not unique sequences derived from the breakpoint region. However, the study proves that APL cells are capable of being recognized and killed in vivo by adaptive immune responses, suggesting that therapeutic vaccines should be possible for this disease when relevant tumor-specific antigens are identified.