Targeted Therapy To SCID Mice With Human Acute Myelocytic Leukemia Using GM-CSF-MA Liposomeons

Objective To prepare GM-CSF-MA immunoliposomes and observe its effect on leukemia cells for providing the preclinical data for futher study. Method 1.GM-CSF-MA immunoliposomes were prepared by reverse-phase evaporation (REV). 2.SCID mice with human acute myeliod leukemia model was established by injecting HL-60 cells through tail vein. The leukemia model was verified by morphology,immunology and pathology. 3.SCID mice with human AML were randomly divided into 3 groups treaded by GM-CSF-MA immunoliposome,MA-liposome and MA respectively. Another 2 groups was control. HL-60 cells in blood and marrow were counted and survival time of the SCID mice was calculated to evalue the therapeutic efficacy of GM-CSF-MA immunoliposome; changes of AST,ALT,BUN,Cr and CK were detected and histopathology of liver,spleen,kidney,lung and heart in amort animal were examined. Result 1.The encapsulation efficiency of MTZ and Ara-C was 80.1% and 84.2%, and the coupled efficiency of GM-CSF was 54.0%. 2.Typical human AML leukemia model were established successfully in all SCID mice. 3.All treatment groups had marrow inhibition with the decrease of peripheral WBC at the beginning of treatment. But 3weeks after treatment, The peripheral WBC of groupâ… begin to recover, at the same time RBC and PLT had already recovered to normal, while groupâ…¡,â…¢were still in the stage of marrow inhibitory. After 2 weeks of treament, HL-60 cells in Peripheral blood and marrow in treatment group began to decrease, especially in groupâ… , however those in control groups were increased. survival time of treatment groups were longer than control groups and groupâ… were longer than groupâ…¡,â…¢. 4.AST,ALT,BUN and Cr increased in all mice with human AML before treament. The AST,ALT,BUN and Cr in groupâ… were obviously decreased while creatase had not marked changes, however those in groupsâ…¢were increased. Hepatomegaly and splenomegaly could be found in some amort mice and infiltration of HL-60 cells in the liver and spleen could be verified by biopsy of articulo mortis mice were disparity increasing. Conclusion GM-CSF-MA immunoliposomes have obvious therapeutic efficacy on acute myeloid leukemia model, and have less toxicant side effect than MA. GM-CSF-MA immunoliposomes is a high effective,low toxical new method on targeted therapy on acute myeloid leukemia.