Antibody Engineering Cuts the Collateral Damage of Cancer Drugs

Mon, Aug 25, 2008


Killing cancer cells, while leaving normal tissue unscathed, is almost impossible.

Nanotechnology may do the trick, but big pharmaceutical companies are far from embracing that strategy. In the meantime, highly-engineered biological molecules will fill the void.                                                    

Antibodies can recognize cancer cells, and latch onto them, but they won’t kill their targets without some help.

By attaching powerful poisons onto the cancer-seeking antibodies, scientists can make smart drugs that hit diseased cells hard.

When injected into the body, the Y-shaped molecules drift around until they latch onto abnormal cells, and then their toxic payloads kill them. But it turns out that they also cause quite a bit of collateral damage — like liver and kidney irritation.

Researchers at Genentech have found a way to reduce those side effects.

William Mallet, Jagath Junutula, and their colleagues invented a trick to precisely control how many of the cell-killing compounds become bonded to each antibody, and then they tested the carefully crafted drugs on mice, rats and monkeys.

In the current issue of Nature Biotechnology, Mallet and Junutula explain that attaching lots of toxic molecules onto each antibody is not the best idea. One or two poison molecules per protein will suffice.

Image: National Library of Medicine


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