A nanotechnology therapy that targets cancer with a “stealth smart bomb” is to begin patient trials next year in the first clinical test of a pioneering approach to medicine, The Times has learnt.
The nanoparticle, which targets tumour cells while evading the body’s immune system, promises to deliver larger and more effective doses of drugs to cancers, while simultaneously sparing patients many of the distressing side-effects of chemotherapy.
Animal studies have indicated that the treatment can shrink tumours “essentially to zero”, while being better tolerated than conventional cancer treatments. Final toxicology studies are about to begin.
A trial involving about 25 cancer patients is scheduled to start within a year. If successful, it could lead to a licensed drug within five years.
Although the therapy was originally designed for prostate cancer, it is expected to be effective against other solid tumours, such as forms of breast, lung and brain cancer. Patients with some of these cancers, as well as prostate cancer, may be included in the first trial.
The technology, developed by BIND Biosciences, a company based in Cambridge, Massachusetts, should also be suitable for delivering drugs for treating other conditions, as well as for the chemotherapy agents that it has been set up to carry.
The nanoparticle, known as BIND 014, is designed to solve three of the major challenges in drug delivery: how to ensure therapeutic molecules get to the right place in the body, how to release them slowly over several days, and how to keep the body’s immune system from recognising them as foreign and destroying them.
It does this by packing drugs inside a “special delivery parcel” developed by Robert Langer, of the Massachusetts Institute of Technology, and Omid Farokhzad, of Harvard University, who founded BIND Biosciences.
This nanoparticle’s diameter is 1,000 times smaller than that of a human hair, measuring about 100 nanometres — or one ten-millionth of a metre — across. It has four elements, the first of which is its payload, a common chemotherapy drug called docetaxel or Taxotere.
The docetaxel molecules are enclosed in a matrix made of a biodegradable polymer known as polylactic acid, which breaks down slowly over several days so that the drug is released gradually. This means that a single injection of nanoparticles can have a long-lasting effect.
This drug-filled “warhead” is then covered with a “stealth coating” of polyethylene glycol, which helps the particle to hide so that it is not attacked by elements of the body’s immune system such as antibodies and macrophage cells. Normally, nanoparticles for drug delivery risk being recognised by the immune system and destroyed.
“Regular nanoparticles struggle to get through to tumours,” Professor Langer said. “They get eaten by macrophages. By containing the drug within this molecule, we can avoid the macrophages.”
The final element of the particle is its smart targeting system, in the form of special enzymes attached to the outer coating known as targeting ligands. These are designed to bind to a molecule found on prostate cancer cells called prostate-specific membrane antigen (PSMA), so that the particles accumulate at the site of tumours before releasing their drugs.
Professor Langer said: “We’ve created a nanoparticle decorated with two molecules, one of which helps it to dodge the immune system, while the other helps it to target cancer cells.”
The drug has been successfully tested against human prostate tumours grown under the skin of mice, in studies that have shown both that the drug accumulates around tumours and reduces them in size. “It’s shrunk tumours in animals essentially to zero,” Professor Langer said.
As the PMSA molecule targeted by the nanoparticle is also found in the blood vessels grown by many other solid tumours, it should be suitable for treating other cancers.
“We think that going after that same targets with that same drug, we can not only go after prostate cancer but a considerably long list of other solid tumours,” Dr Hrkach said. “The plan is to start clinical trials in the third quarter of next year. We’re now transferring our efforts to manufacturing enough material for a clinical study.”
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The Times (abridged)