CAMOUFLAGING artificial antibodies so they can evade the watchful eyes of our
immune system could speed the development of treatments for everything from
rheumatoid arthritis to cancer.
Antibodies are proteins made by the immune system that bind to specific
targets. They can latch onto toxins, viruses and bacteria, rendering them
harmless or marking them out for destruction.
Their ability to home in on specific proteins means synthetic antibodies
could be valuable weapons against a wide range of diseases. Attach a drug to the
right antibody and you can deliver it to a diseased tissue, for example. 鈥淭he
market for them is huge,鈥� says Daniel Ozanne of biotech company Biovation in
Aberdeen.
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Yet of the 400 or so synthetic antibodies in development, only 10 have so far
been licensed for use in the US. One reason is that the standard method of
mass-production relies on getting mice to generate antibodies to the target. Our
immune system sees these antibodies as foreign proteins and will attack them.
This not only neutralises the therapy, it can also cause allergic reactions,
including life-threatening anaphylactic shock.
In recent years, scientists have been able to largely disguise these
antibodies by pasting bits of the gene coding for human antibodies into the
mouse equivalent. However, the vital part of the mouse antibody that recognises
and sticks to its target has to be left untouched. So even these engineered
antibodies can provoke an immune response, albeit a reduced one.
But researchers at Biovation have now found a way to 鈥渃loak鈥� these telltale
parts by working out which bits can be spotted by the immune system. When a
patrolling immune cell discovers a foreign protein, it chops it up into little
pieces and presents these to the T cells, the commanding officers that
coordinate any immune attack. But the patrol cells can only present pieces of
protein that stick to a molecule called MHC II.
Biovation鈥檚 鈥淒eImmunisation鈥� technology uses computer programs to predict the
basic structure of the key pieces of an antibody and check to see if they would
stick to any of a wide range of known MHC IIs. Molecular biologists can then
tweak the structure of these fragments to give MHC II the slip. In preliminary
trials of an antibody against prostate cancer that was tailored this way, says
Ozanne, none of the 35 patients reacted badly.
鈥淚t鈥檚 a very clever idea,鈥� says Martin Glennie, an immunochemist at the
University of Southampton. Researchers are now developing human antibodies in
the test tube, he says, but even a fully human antibody can provoke immune
reactions, especially if administered repeatedly to treat a long-term problem.
鈥淚t makes a lot of sense to try and reduce [reactions] to a minimum,鈥� says
Glennie.