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LFA3-Ig融合蛋白是由人淋巴细胞功能相关抗原3(LFA-3)与CD2结合的部分与人IgG1的Fc段构成的融合蛋白,采用基因工程技术大量制备,可用于治疗银屑病等自身免疫性疾病。实验利用体外细胞模型及正常食蟹猴作为体内模型,研究了上海市抗体工程技术研究中心研制和中试生产LFA3-Ig的生物学效应。结果表明:rhLFA3-Ig可通过特异性地结合淋巴细胞表面的CD2,抑制T淋巴细胞的活化,其体外活性与国外同类产品相比无显著差异;食蟹猴重复应用rhLFA3-Ig后,高剂量组外周血淋巴细胞有显著下降,于给药后48 h即降至最低,为给药前的76.1%;给药期间高剂量组外周血淋巴细胞波动于给药前的80%左右,至恢复期末,淋巴细胞恢复至给药前的90%左右。给药后,各剂量组CD2+、CD3+、CD4+及CD8+淋巴细胞计数均有不同程度的下降,且具有剂量相关性,停药后可恢复。上述结果为该重组融合蛋白提供了必要的临床前药效学资料,可作为其临床试验的重要参考。
The LFA3-Ig fusion protein is a fusion protein composed of the part of human lymphocyte function-related antigen 3 (LFA-3) bound to CD2 and the Fc part of human IgG1, which is prepared by gene engineering technology and can be used for treating psoriasis and other self Immune disease. The in vitro cell model and normal cynomolgus monkeys were used as experimental models to study the biological effects of LFA3-Ig produced and developed by Shanghai Antibody Engineering and Technology Research Center. The results showed that rhLFA3-Ig could inhibit the activation of T lymphocytes by specifically binding to CD2 on the surface of lymphocytes. The in vitro activity of rhLFA3-Ig showed no significant difference compared with that of similar foreign products. After repeated administration of rhLFA3-Ig, Group of peripheral blood lymphocytes decreased significantly, 48 h after administration to a minimum, to 76.1% before administration; high dose group during administration of peripheral blood lymphocytes in the pre-dose of about 80% until the recovery At the end of the period, lymphocytes recovered to about 90% before administration. After administration, the counts of CD2 +, CD3 +, CD4 + and CD8 + lymphocytes in each dose group all decreased in different degrees and had dose-related relationship, and recovered after withdrawal. The above results provide the necessary pre-clinical pharmacodynamic data for the recombinant fusion protein, which can be used as an important reference for clinical trials.