Superantibodies that can bind to targets within cells, rather than on their surface, could lead to a new range of treatments for diseases, a biotech company claims in a report by New Scientist this week.
"Most good targets for diseases are inside cells," says Charles Morgan, president of InNexus Biotechnology of Vancouver, Canada, which has developed the superantibody technology.
Superantibodies could be used to target bacteria and viruses (including HIV) inside cells, for instance, or abnormal proteins that turn cells cancerous. In theory, they could do everything that the small molecules of most conventional drugs do, and more.
The beauty of a cell-penetrating superantibody is that it would be highly discriminating. Because antibodies can be far more specific than small-molecule drugs, and because they are not inherently toxic, they should have fewer side effects. The big disadvantage is that antibodies have to be injected as they do not survive in the stomach.
Antibody-based treatments are already being used to treat diseases in several ways. Over a dozen are now approved for use in people. However, like natural antibodies, all bind to molecules on the surface of cells or viruses.
Antibodies under development can ferry other substances into cells, such as the toxin ricin, and they are sometimes engulfed by a cell after binding to its surface proteins, but none can enter cells freely and target molecules inside them.
However, InNexus says a simple chemical modification enables any antibody to flit in and out of cells until it finds its target. The "key" that allows them to enter is a short protein segment called a membrane-translocating sequence (MTS), normally found in signalling proteins such as growth factors that can enter cells.
Several groups worldwide have shown that attaching MTS segments to other proteins allows them to enter cells. "We thought, can you do this with an antibody?"
Says Morgan, who presented the technology at a BioVentures biotech conference in London earlier this month. InNexus found a way to attach an MTS segment to a structure common to all antibodies.
"And lo and behold, it worked," he says.
Experiments with a fluorescently labelled superantibody show it enters all cells but accumulates only inside cells containing its target, Morgan says. He thinks the antibodies could last in the body for up to a month, entering and leaving cells until they find their target.
As a proof of principle, the company developed a superantibody that binds to and blocks caspase-3, an enzyme inside cells that triggers cell suicide. The superantibody stopped human white blood cells from killing themselves when they were exposed to actinomycin D, a drug that normally triggers cell suicide (Apoptosis, vol 8, p 631).
InNexus hopes a superantibody of this kind can be developed to block cell death in people who have just had heart attacks or strokes. Some researchers have their doubts.
"A lot of work has been done trying to make antibodies that are stable in cells," says Andrew Bradbury of the Los Alamos National Laboratory in New Mexico. "But it's proved far more difficult than expected."
But Morgan says an antibody's stability depends on how it enters the cell. Those that are engulfed after binding to surface proteins end up in structures called endosomes, where they are likely to be destroyed. Superantibodies, however, enter the normal, safe environment of the cell.
"There would definitely be loads of new targets if it worked," says Daniel Elger of biotech company Antisoma, based in London, which has developed an anti-cancer antibody that carries an enzyme into cells after binding to a surface receptor.
But for purposes like blocking viral replication, the success of cell-penetrating superantibodies will depend on the concentrations they reach inside cells. "It would be down to the practicality of whether you could get enough in," he says.
This article will appear in the April 17 edition of New Scientist
Subscribe To SpaceDaily Express
A Black Box for People
Huntsville - Apr 13, 2004
When planes have a problem, analysts can usually figure out what went wrong. They simply check the plane's "black box," which records exactly what was happening to the plane at the time.
|The content herein, unless otherwise known to be public domain, are Copyright 1995-2016 - Space Media Network. All websites are published in Australia and are solely subject to Australian law and governed by Fair Use principals for news reporting and research purposes. AFP, UPI and IANS news wire stories are copyright Agence France-Presse, United Press International and Indo-Asia News Service. ESA news reports are copyright European Space Agency. All NASA sourced material is public domain. Additional copyrights may apply in whole or part to other bona fide parties. Advertising does not imply endorsement, agreement or approval of any opinions, statements or information provided by Space Media Network on any Web page published or hosted by Space Media Network. Privacy Statement All images and articles appearing on Space Media Network have been edited or digitally altered in some way. Any requests to remove copyright material will be acted upon in a timely and appropriate manner. Any attempt to extort money from Space Media Network will be ignored and reported to Australian Law Enforcement Agencies as a potential case of financial fraud involving the use of a telephonic carriage device or postal service.|