抗CD3/抗B细胞肿瘤的双功能小抗体的抗肿瘤活性研究

In vitro and in vivo Anti-tumor Activity of Anti-CD3/Anti-B cell Carcinoma Bispecific Antibody

为评价已研制的抗CD3/抗B细胞肿瘤 (CD2 0 + )双功能小抗体的生物学活性 ,采用多种实验方法在体内外对其进行研究。结果表明 :该型双功能小抗体能同时与Ju rkat和Daudi细胞结合 ,并交联两种细胞形成玫瑰花环。它与Jurkat(CD3+ )和Daudi细胞 (CD2 0 + )的结合的亲和常数Ka分别为 3.2× 10 8M- 1和 8.9× 10 8M- 1。在体外该抗体能激活并介导T细胞杀伤Daudi细胞。裸鼠体内分布实验结果表明 :该型抗体可在移植瘤部位富集 ;在人B淋巴瘤裸鼠移植瘤腹腔模型中 ,联合人的PBMC和IL 2 ,该抗体可以杀灭人B淋巴瘤细胞 ,明显延长荷瘤裸鼠的生存时间。

In order to evaluate the biological activity of the anti-CD3/anti-B cell carcinoma(CD20+) bispecific antibody prepared by our lab, lots of experimental methods were used to analyze it both in vitro and in vivo. The results from current research are shown as follows: this kind of engineering anibody could bind to Jurkat cell(CD3+) and Daudi cell(CD20+) simultaneously, and by that way the antibody was capable of cross-linking those two types cells to form cellular resetting, the affinity constant(Ka) of them were 3.2×108M -1 and 8.9×108M -1, respectively. In vitro, the engineering antibody could efficiently activated human T cell to lyse B lymphoma cells in a dose-dependent manner. In vivo, 125I labeled anti-CD3/anti-CD20 antibody localized preferentially in subcutaneously implanted Raji tumor(CD20+) in nude mice, and in a separate study, administered along with IL-2 and T-riched human PBMC, the antibody could recruited T cells to kill B lymphoma cell(CD20+) and inhibited the growth of xenografted human B lymphoma in the nude mice, and significantly prolonged the survival of tumor-bearing nude mice.