They could be adapted to target virtually any tumour tissue in the body, and could put an end to many of the toxic side effects associated with chemotherapy drugs because they do not release their payload until they are inside the target cell. This also means that far less drug is required.
The EDVs are able to selectively target different tissues thanks to bispecific antibodies attached to their surface. One arm of the antibody is specific to the EDV and is connected via a linker molecule to the second antibody, which is specific to a protein on the target tissue – for example, the Her2 receptor on breast cancer cells, which is also targeted by Herceptin.
Targeting is also aided by the fact that the blood vessels supplying cancer cells are often leaky, and by coincidence the 400 nanometre EDVs are the perfect size to fall through these holes into the tumour tissue. “Within 2 hours of intravenous administration greater than 30% of the dose ends up in the tumour microenvironment” says Brahmbhatt, who presented the findings at RNAi 2007 in Boston, Massachusetts, on 3 May.
Once EDVs bind to the correct cells, they are internalised and broken down – releasing the drug into the cell, where it can take effect.
EnGeneIC hopes to begin human trials towards the end of 2007.
“We haven’t yet found a drug that you couldn’t load,” says MacDiarmid, and EnGeneIC believes EDVs could enable cancer patients to be given high doses of multiple drugs, thus increasing the chances of finding one that works for them. Oncologists are often reluctant to prescribe multiple drugs because of the risk of serious side effects – and if they do they will usually reduce the doses to limit the toxicity.
“The amount of drug given with EDVs is thousands of fold less than if they were given directly,” says Bruce Stillman, director of Cold Spring Harbor Laboratory in New York, US, and an advisor to the EnGeneIc team. “This, coupled with the fact that you can also target the drugs directly to the target tissue, means that the reduction in side effects could be extraordinary.”
Preliminary results in mice also suggest that EDVs could also be used to deliver novel therapies like RNA interference (RNAi), where one of the major hurdles is finding a targeted delivery method.
This would be a great advance for fighting cancer and to speed up and make RNA interference and gene therapies more effective.