Treatmen of kidney cancer in mice with haploidentical bone maraaow cell transplantation

Objective To study the effect of chimerism level on graft-versus-tumor（GVT） and graft-versus-host disease（GVHD） after haploidentical bone marrow cell transplantation and its mechanism. Methods Twenty-five 8-12 weeks old BALB/c mice were randomly divided control group（group C,n=5）,mixed chimerism group（group A,n=10）,full donor chimerism group（group B,n=10）.Mice in group C were only inoculated with Renca cells（2.6×10⁶）.Mice in group A were irradiated at the dose of 4Gy,infused with bone marrow cells（5×10⁶） from CB6F1 mice on day 1,and inoculated with Renca cells（2.6×10⁶） on day 8.Mice in group B were were irradiated at the dose of 8Gy,infused with bone marrow cells（5×10⁶） from CB6F1 mice on day 1,and inoculated with Renca cells（2.6×10⁶） on day 8.Tumor growth was monitored every 4 days.Chimerism levels in groups A and B were measured with a FACScan cytometer on days 14,21,and 28 after haploidentical bone marrow cell transplantation.Tumor-bearing mice were killed 32 days by decapitation with the tumor isolated and weighed.Interleukin-2（IL-2） and interferon gamma（IFN-γ） levels in plasm were measured by ELISA.Liver,skin,and intestine,were cut into sections which were stained with H＆E to observe GVHD,Tumor tissues to observe area ratio of tumor necrosis. Results The mixed chimera level reached its peak in groups A and B 2 weeks after haploidentical bone marrow cell transplantation,and decreased to less than 10% in group A 3-4 weeks after haploidentical bone marrow cell transplantation but remained over 90% in group B 4 weeks after haploidentical bone marrow cell transplantation.The tumor growth was significantly slower and the tumor weight was notably less in the group B than in groups A and C（P＜0.01）.The tumor suppressing rate was 52% for group B.The levels of IL-2,IFN-γ and the area ratio of tumor necrosis were significantly higher in group B than in groups A and C（P＜0.01）.No significant change occurred in GVHD of liver,intestine and skin. Conclusion Haploidentical allogeneic bone marrow cell transplantation at full donor chimerism level may stimulate the systemic GVT immunity and inhibit tumor growth in mice by increasing tumor necrosis.