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应用单克隆抗体导向药物前体活化酶裂解药物前体,从而在体内释放出有活性的细胞毒性药物用于治疗癌症,已成为一种很有希望的抗体导向酶药物前体疗法(ADEPT)。ADEPT已成功地用于阻止人肿瘤在小鼠异种移植模型中的发展。因此,为满足临床试验的要求,需制备数克量的抗体—酶结合物。同时为了获得最大产量的蛋白和使酶活性及抗原结合活性的丧失降低到最小程度,增大结合物的产生,对所用化学偶联过程的重新评价具有重要意义。本文中作者选用了偶联在CPG2单克隆抗体A587的F(ab′)2片段来制备结合物,以增加对组织的穿透作用和达到对肿瘤特异性定位的最佳性能。
The use of monoclonal antibody-directed prodrug-activated enzyme to cleave drug precursors to release active cytotoxic drugs in the body for the treatment of cancer has become a promising antibody-directed enzyme prodrug (ADEPT). ADEPT has been successfully used to prevent the development of human tumors in a mouse xenograft model. Therefore, in order to meet the requirements of clinical trials, several grams of antibody-enzyme conjugate should be prepared. At the same time, in order to obtain the maximum yield of protein and to minimize the loss of enzyme activity and antigen binding activity and to increase the production of conjugates, it is of great significance to reevaluate the chemical coupling process used. The authors selected F (ab ’) 2 fragments conjugated to the CPG2 monoclonal antibody A587 to prepare conjugates to increase tissue penetration and achieve optimal performance for tumor-specific localization.