Prasad提醒,带有MMAE等强效非特异性载荷的ADC可能仅靠载荷起效,需要额外证据才能证明新型靶向部分的作用。
如果你做了一个新药,但把它连接到MMAE或强效放射性同位素上,要注意载荷可能在杀死一个细胞之后或之前就被切断,载荷本身就能杀死癌细胞。足够高剂量的活性载荷ADC在靶点之外的地方也会起作用。微管抑制剂对很多癌症都有效。要让我相信新型ADC起了关键作用,需要额外的证据。原文 (en)
If you make a new drug but tether it to MMAE or a powerful radioisotope, note that the payload can be cleaved after killing one cell, or before, and the payload can do cancer killing all by itself. A high enough dose of an ADC with active payload will work in other places besides the target. Microtubule inhibitors work in a lot of cancer. It takes extra to persuade me that the novel ADC is critical to that.