融合蛋白anti-CD19（Fab）-LDM对B细胞淋巴瘤的抑制作用

Inhibition of fusion protein anti-CD19（Fab）-LDM on B-cell lymphoma

目的：探讨融合蛋白anti-CD19（Fab）-LDM在体内对B细胞淋巴瘤生长的抑制作用。方法利用流式细胞检测技术分析anti-CD19（Fab）-LDP抗体与B型淋巴瘤细胞体外免疫结合活性，并分析其平衡解离常数。建立Balb/c裸鼠Raji细胞移植瘤模型，活体成像技术观察Cy5标记的anti-CD19（Fab）-LDP在裸鼠体内靶向定位作用。将融合蛋白anti-CD19（Fab）-LDM经尾静脉注射入Raji荷瘤裸鼠体内，观察其对肿瘤生长的抑制情况，计算抑瘤率，评价疗效。结果 anti-CD19（Fab）-LDP抗体与靶抗原的亲和活性与anti-CD19（Fab）抗体相当，两者的平衡解离常数分别为3.3＆#215;109M-1和4.3＆#215;109M-1。成功建立Raji淋巴瘤细胞皮下移植瘤模型，体内活体成像结果表明，融合蛋白anti-CD19（Fab）-LDP可靶向定位到肿瘤部位。融合蛋白anti-CD19（Fab）-LDM对裸鼠移植性CD19＋B细胞淋巴瘤的生长具有抑制作用，并且具有剂量依赖性。结论融合蛋白anti-CD19（Fab）-LDM，具有较强的特异抗肿瘤疗效，作为抗体靶向药物，在B系淋巴瘤治疗中具有很好的应用前景。

Objective To investigate the inhibition of the fusion protein anti-CD19（Fab）-LDM on B-cell lymphoma. Methods Using flow cytometry to analyze the in vitro immunological binding activity of anti-CD19（Fab）-LDP antibody and B-cell lymphoma cells and its dissoci ation constant. The Raji cell xenograft model in Balb/c nude mice was established. The target position of Cy5-labeled anti-CD19（Fab）-LDP in nude mice was determined by in vivo imaging. The fusion protein anti-CD19（Fab）-LDM was injected into Raji tumor-bearing nude mice through caudal vein. Its inhibition on tumor growth was determined,the inhibition rate was calculated,and the effect was evaluated. Results The affinity between anti-CD19（Fab）-LDP antibody and the target antigen was similar with anti-CD19（Fab）antibody,and the dissociation constants were 3.3 ＆#215; 109M-1 and 4.3 ＆#215; 109M-1,respectively. The subcutaneous Raji cell lymphoma xenograft model was successfully established. The findings of the in vivo imaging showed that the fusion protein anti-CD19（Fab）-LDP could be targeted to the tumor site.The fusion protein anti-CD19（Fab）-LDM could inhibit the growth of the transplanted CD19＋ B cell lymphoma with dose dependency. Conclusion The fusion protein anti-CD19（Fab）-LDM,as an antibody-targeted drug,has significant and specific anti-tumor effect, which has a good application prospect in the treatment of B-cell lymphoma.