Edible antibodies

Two new pieces up in the February issue of Nature Biotechnology. The first is a short news piece about the synthetic biology regulatory recommendations from the Presidential Commission for the Study of Bioethical Issues, which was mostly remarkable in that everybody I spoke to seemed pretty darn satisfied with them, which is always a pleasant surprise when it comes to government oversight of research.

The other is a much longer feature about new ways of getting antibody and antibody-like drugs into the body, as an alternative to making patients sit through a 4-hour IV drip every week or so… especially for cases where you’re just trying to target a particular tissue or organ, and don’t necessarily want to dump tremendous amounts of antibody into the bloodstream to hit it. This was pretty interesting stuff for me, since I don’t venture into the pharma world too much, but I was a bit sad that one of my favorite parts of the piece had to be cut due to my old arch-nemesis, length constraints. A quick overview of the cut section after the jump…

Most people have assumed for a long time that you can’t simply take an ‘antibody pill’, even to target digestive tract problems, simply because the gut offers such an inhospitable environment for naked proteins. Some of the antibody-ish proteins I touch on in my article are made of much sturdier stuff, though, and can handle even prolonged exposure to very acidic conditions at body temperature. Belgian company Ablynx has been using tiny chunks derived from camel and llama antibodies, which are already far simpler and more compact than mouse or human antibodies, and they’ve shown that mice can be treated orally for Crohn’s disease with their ‘nanobodies’.

Image from Ablynx website.

Two other groups have been doing some pretty nifty stuff with engineered strains of fermenting bacteria. Lennart Hammarström and his colleagues at the Karolinska Institute in Sweden have chosen Lactobacillus bacteria as their vehicle – these are bugs that are probably already in your body right now, and have a starring role in the production of some of my favorite consumables, including yogurt, beer and kimchi.

Thanks, Lactobacillus! (image from Flickr user titanium22)

By engineering these bacteria to produce nanobodies, they can be turned into drug delivery vehicles that stably – but harmlessly – persist in the body after being consumed, pumping out therapeutic compounds to treat chronic conditions. Hammarström told me, “We have made Lactobacilli that are directed against P. gingivalis, which makes you lose your teeth to periodontitis; we have been doing it against pathogens of the gut, and now we are targeting pathogens of the vagina.” The idea is that these would ultimately be translated into food-grade formulations, where the bacteria carry no foreign DNA except for the nanobody gene – which would be safely embedded in their chromosomal DNA. “People drink camel milk that contains [antibodies], and so there’s nothing really strange there,” said Hammarström. He adds that his team has been filing paperwork for a clinical trial that will hopefully launch this year, as a component of the EU 7th Framework Programme-supported Lactobody Project.

Another Belgian company, ActoGeniX, is using a different bacterium, the all-star cheesemaker Lactococcus, as its delivery-boy. Like Lactobacillus, these bacteria are relatively straightforward to cultivate and engineer, but Lactococcus is not a long-term resident of the human gut, offering the potential advantage that they won’t linger indefinitely after ingestion. I spoke with their director of preclinical operations, Pier Rottiers, who told me, “We have a library of more than 90  different Lactococci secreting different kinds of therapeutics.” They’ve got an ongoing clinical trial for addressing oral mucositis, a nasty side-effect of therapy in cancer patients. They’ve also published a study where their bacteria produced anti-inflammatory nanonbodies that helped counter symptoms in a mouse model of colitis. “We could demonstrate that they were effective to block their antigen, and could therefore heal a disease,” said Rottiers.

It’s a big plus that both bacteria are already being consumed by people on a daily basis, which should hopefully smooth their progress through clinical trials, although – given the often-irrational fear and panic surrounding GMOs – both researchers are highly aware of the issue of public perception. “For some people, ‘genetically-modified organisms’ is a dirty word,” said Hammarström. “I think we may have to wait a little bit more before the public is ready to take this on.”

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