Technology: Human disguise for tumour-busting toxins

 作者:宁妞舜     |      日期:2019-02-28 02:03:01
By ANDY COGHLAN Mouse antibodies with a human look may emerge as the next generation of warriors in the fight against lung cancer and a type of leukaemia. Clinical trials of the anti-bodies are now under way in the US. Scientists genetically engineered the mouse antibodies so that their surface amino acids resemble human ones. This should stop the patient’s immune system from perceiving them as ‘foreign’ and so attacking them. The antibodies could also be used to carry strong toxins such as ricin as ‘ammunition’ in attacking tumour cells, while leaving healthy cells unharmed. ‘Inside, it’s a mouse antibody, but on its surface it looks human,’ says Tony Rees, the executive technical director of Oxford Molecular, a computer-aided molecular design company based in Oxford. Rees and his team worked out how to disguise the antibodies through a technique they call ‘resurfacing’. The company started with two kinds of mouse antibody, both of which bind strongly to human tumour cells. The company hopes that this characteristic can be exploited by giving the antibodies strong toxins as ‘baggage’ for delivery to tumour cells. Such deliveries would be impossible, however, if the mouse antibodies were ‘found out’ and attacked by a patient’s immune system. Rees and his team used software to work out the differences between the amino acids on the surfaces of the two mouse antibodies, and those of typical human antibodies. These differences give each species’ cells a characteristic appearance at the molecular level. Using this data, they determined which surface features had to be changed to ‘fool’ the human immune system. These changes were then genetically engineered by ImmunoGen, a biotechnology company in Cambridge, Massachusetts. Engineers at ImmunoGen made a synthetic version of the genetic instructions required to produce mouse antibodies with the human arrangement of amino acids. They put this into live monkey kidney cells, which produced the resurfaced antibodies in fermenters. In laboratory tests,