多价抗人精浆蛋白/抗CD_3双特异性单链抗体的活性研究

Study on biologic activity of multivalent bispecific single chain antibody specific for human γ-seminoprotein and CD_3 molecule

目的探讨多价抗人精浆蛋白/抗CD3双特异性单链抗体的生物学活性。方法利用流式细胞仪和51Cr释放试验评价多价双特异性单链抗体的抗原亲和活性和体外介导杀伤靶细胞的效果。利用母性BALB/C裸鼠前列腺癌模型分析多价双特异性单链抗体在体内介导细胞毒T淋巴细胞对肿瘤细胞杀伤的能力。结果多价双特异性抗体可以特异性结合表达PSA的前列腺癌细胞和CD3阳性淋巴瘤细胞,阳性结合率分别为74%和83%。在体外,有细胞毒T淋巴细胞存在时多价抗体可引起前列腺癌细胞裂解。与对照组比较,接种前列腺癌细胞的裸鼠在注射激活的细胞毒T淋巴细胞的同时接受多价抗体治疗后,肿瘤生长明显受到抑制(P<0.05)。结论多价抗人精浆蛋白/抗CD3双特异性单链抗体具有良好的生物学活性,在体内外均可以介导细胞毒T淋巴细胞对靶细胞的杀伤。

Objective To study the biologic activity of multivalent bispecific single chain antibody specific for human γ-seminoprotein and CD_3 molecule. Methods Flow cytometry (FCM) was used to detect the binding activity of the antibody to CD_3-positive cell line Jurkat and prostate carcinoma cell line LNCaP.The efficacy of the antibody in mediating tumor cell lysis in vitro was determined by using the chromium 51 -release test.For in vivo evaluation of the antibody’s activity,a nude mouse model was used.The mice we...