体外研究抗CD20单克隆抗体对骨髓瘤细胞的细胞毒性作用

目的:体外探讨上调多发性骨髓瘤(MM)细胞表面CD20抗原表达后,抗CD20单克隆抗体美罗华对骨髓瘤细胞的细胞毒性作用。方法:将浓度为(0-800)×10³U/L的重组人干扰素γ(hrγ-IFN),分别与10例初治(初治组)和10例复发难治(难治组)的MM患者瘤细胞共同培养,流式细胞仪测定培养前后瘤细胞表面CD20的表达;应用MTT比色法分析不同浓度美罗华对CD20抗原表达上调后瘤细胞的抗体依赖性细胞介导的细胞毒作用(ADCC)和补体依赖性细胞毒作用(CDC)。结果:hrγ-IFN浓度分别≥5×10⁴U/L或≥1×10⁵U/L,可明显增加初治组或难治组瘤细胞表面CD20的表达,在用8×10⁵U/Lhrγ-IFN上调瘤细胞表面CD20抗原的表达后,12mg/L和16mg/L的美罗华分别能显著介导初治组和难治组效应细胞对MM瘤细胞的ADCC和激活CDC。结论:体外hrγ-IFN上调MM瘤细胞表面CD20的表达后、抗CD20单克隆抗体美罗华具有对瘤细胞的ADCC和CDC效应。

Study of cytotoxicity of anti-CD20 monoclonal antibody against myeloma cells in vitro

AIM: To observe the cytotoxicity on myeloma cells mediated by anti-CD20 monoclonal antibody-mabthera, after heightening level of CD20 expression on myeloma cells membrane by γ-interferon. METHODS: 10 untreated(UT) and 10 relapsed or refractory(RR) MM patients'myeloma cells were cultured with human recombinant γ-interferon (hrγ-IFN) at concentrations of (0-800)×10³ U/L to heighten level of CD20 expression, then complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) on myeloma cells mediated by mabthera were studied through MTT methods. RESULTS: When CD20 expression of UT MM and RR MM patients' myeloma cells increased after treated by hrγ-IFN, 12 mg/L and 16 mg/L mabthera mediated ADCC and CDC against myeloma cells in group UT patients and group RR patients, respectively. CONCLUSION: After heightened level of CD20 expression on myeloma cells membrane by hrγ-IFN, mabthera mediated ADCC and CDC against myeloma cells in vitro.