IMAGINE never having to take a pill again. Instead, mini drug factories hidden inside your bones, and made from your own immune cells, would churn out personalised drugs and other molecules designed to keep you fit and healthy. Such a factory has been created in mice, and could soon be tested in humans to treat HIV.
"We want to turn people's cells into drug factories, giving them the genetic information they need to produce their own treatment," says Matthew Scholz of Immusoft in Seattle, which is developing the technique.
Immusoft is focusing on B-cells, a component of the immune system. One of their roles is to produce antibodies against infections or unwanted foreign substances such as toxins.
In 2009, David Baltimore and colleagues at the California Institute of Technology in Pasadena showed that stem cells from bone marrow could be engineered to develop into B-cells that made antibodies against HIV (Blood, doi.org/dwm53t).
The Immusoft researchers have built on that work, extracting immature B-cells called plasmoblasts from human blood and treating them with a virus that inserts the genetic code for a new protein (see diagram). When the modified cells were injected into the bloodstream of mice, some migrated to the bone marrow. Here they began making the proteins they had been engineered to make – a class of so-called broadly neutralising antibodies against HIV.
"I think this is potentially very important," says Carl June at the University of Pennsylvania, Philadelphia, who has been engineering another part of the immune system, T-cells, to fight HIV. "But whether this has clinical use depends on the efficiency of gene transfer, expression and secretion of the antibody, and most importantly the level of secreted protein in body fluids."
"If they can achieve therapeutic levels of antibody, this could be a real advance in cellular therapy," Baltimore says.
One of the remaining challenges is to ensure that the correct amount of antibody is produced. "The risk of too little or too much has to be considered," says Michel Sadelain of the Memorial Sloan-Kettering Cancer Center in New York, who has engineered T-cells to fight cancer.
It's also not clear how long the engineered B-cells can be made to survive. In the tests on mice, many of the cells died, but some were still alive 100 days later. "It's a very attractive idea to supply stable levels of antibodies from a cellular source in the body. The challenge is finding the right cell that would persist for the desired amount of time – days, or years in some cases – and that's a big challenge," Sadelain says.
The next step is to try injecting the modified B-cells into people, with Immusoft gearing up to do a trial in HIV-positive adults. If this succeeds, the approach could also be used in children with rare enzyme disorders like mucopolysaccharidosis. These children are unable to make certain enzymes, leading to the breakdown of various tissues, loss of vision and cognitive problems. Untreated, they usually die by the age of 12.
Hamster cells can be harnessed to produce replacement enzymes, but the treatment costs around $250,000 a year and involves regular injections. "For disorders like that, being able to produce the enzyme 24/7 in your body would be a big advantage," says Scholz, who presented the mouse results at the Strategies for Engineered Negligible Senescence meeting in Cambridge, UK, this month.
Ultimately, it might be possible to engineer B-cells to churn out any protein of choice. They could boost levels of hormones that fall as we age, or other substances that keep the body healthy, such as humanin. This protects brain cells against Alzheimer's disease, and is present at higher than average levels in people who live to be 100. "It might be possible to recreate the biochemical environment of youth," Scholz says.
This article appeared in print under the headline "Bones can host mini medicine factories"
- New Scientist
- Not just a website!
- Subscribe to New Scientist and get:
- New Scientist magazine delivered every week
- Unlimited online access to articles from over 500 back issues
- Subscribe Now and Save
If you would like to reuse any content from New Scientist, either in print or online, please contact the syndication department first for permission. New Scientist does not own rights to photos, but there are a variety of licensing options available for use of articles and graphics we own the copyright to.
Have your say
Only subscribers may leave comments on this article. Please log in.
Only personal subscribers may leave comments on this article
All comments should respect the New Scientist House Rules. If you think a particular comment breaks these rules then please use the "Report" link in that comment to report it to us.
If you are having a technical problem posting a comment, please contact technical support.
