ANIBODY-DRUG CONJUGATES FOR CANCER THERAPY

该项目的目的是生产单抗-药物偶联物。 对选择性摧毁人类癌症具有治疗效力 细胞。介绍了目前制备的抗体-药物结合物 这种方法不能在靶细胞内实现高水平的游离药物。 建议取代目前中等细胞毒性的抗癌药物 含有美坦素的药物，其细胞毒性是其100到1000倍。这个 美坦素类化合物将通过二硫键连接，二硫键在 循环，但细胞内分裂。梅坦辛诺将会是 合成修饰以加入二硫基或硫醇基团。最多的 这些药物的细胞毒性将通过以下方式与单抗偶联 二硫键，并评估对癌细胞的体外细胞毒性。在……里面 体内药代动力学特性将在小鼠身上进行评估。

The aim of this project is to produce monoclonal antibody-drug conjugates with therapeutic potency for the selective destruction of human cancer cells. It is stated that antibody-drug conjugates prepared by current approaches do not achieve high levels of free drug inside targeted cells. It is proposed to replace the current moderately cytotoxic anti-cancer drugs with maytansinoids which are 100 to 1000 fold more cytotoxic. The maytansinoids will be linked via disulfide bonds, which are stable in circulation, but cleaved intracellularly. The maytansinoids will be synthetically modified to incorporate disulfide or thiol groups. The most cytotoxic of these drugs will be conjugated to monoclonal antibodies by disulfide bonds and assessed for in vitro cytotoxicity to cancer cells. In vivo pharmacokinetic properties will be evaluated in mice.