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Cytarabine enhances B7 expression on leukemic cells and promotes cytotoxic effect of bispecific antibody against target cells
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Abstract:
Objective:To observe the effects of cytarabine (AraC) on B7 expression on leukemia cells, and to study the effects of antiCD3/antiPgp bispecific antibody on the cytotoxicity of T cells against drugresistant leukemia cells. Methods：The expressions of B71 and B72 on K562 (leukemia cells) and K562/A02 cells (drugresistant leukemia cells) were examined by flow cytometry after treatment with AraC for different periods. B71 and B72 mRNA expressions in K562 and K562/A02 cells were detected by RTPCR. The proliferation of T lymphocytes stimulated by AraCtreated K562 and K562/A02 cells was detected by MTT assay. In vitro cytotoxicity of T lymphocytes against K562 and K562/A02 cells was analyzed using CytoTox 96 nonradioactive method after treatment with antiCD3/antiPgp bispecific antibody and AraC. Results:Compared with untreated cells, B71 and B72 expression on AraCtreated K562 and K562/A02 cells was significantly enhanced. MTT results showed that AraCtreated K562 and K562/A02 cells increased the proliferation of T lymhocytes. AraC combined with antiCD3/antiPgp bispecific antibody enhanced the cytotoxicity of T cells against K562 and K562/A02 target cells (T∶target, 0.39∶125∶1), especially when against Pgp positive drugresistant K562/A02 leukemia cells. Conclusion: AraC can upregulate B7 expression on leukemia cells, and when combined with antiCD3/antiPgp bispecific antibody it can enhance the cytotoxicity of T cells against target leukemia cells in vitro.
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Project Supported:
Supported by the National Natural Science Foundation of China(No. 30701012); the Science and Technology Program of Tianjin (No. 08ZCKFSH04100); the Basic Application Research Program of Tianjin (No. 07JCZDJC04900)
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