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life defined by hazard tape

Having had my morning communte disrupted by the Independent Police Complaints Commission -- SS Mary and John is still sealed off -- and the forest of newshounds around the Military Tribunal, I found half the car-park taped off at work, protestors outside OUP, all that jazz. And now Bush has decided that times simply aren't dangerous enough. Well, that made my day ...

I've been following, like everyone else in the UK, the story of the lab rats who took the drug of doom.

It was the comment of the girlfriend whose panicked face screams progress gone wrong! that "this is something new" that got me wondering. What had they given them? The BBC call it an anti-inflammatory drug, which sounds kind of nice, doesn't it? Fluffy. I've been on them. But how could an anti-inflammatory treat anything except for the symptoms of rheumatoid arthritis and leukaemia?

Off to Parexel, who organised the trial. They explain that "TGN 1412 is an immunomodulatory humanized agonistic anti-CD28 monoclonal antibody". I needed a translation on pretty much every word in that sentence, but probably some of you do not. Agonistic, particularly, had me wondering.

After a few blind alleys, though, I found that the European Medicines Agency Pre-authorisation Evaluation of Medicines for Human Use publish their hearings on the web. Here's the relevant:

Humanised agonistic anti-CD28 monoclonal antibody could be of potential significant benefit for the treatment of chronic lymphocytic leukemia because it may offer a new way of killing cancer cells.

[...]

Antibodies are proteins in the body that target and link specific shapes (the so-called antigens) on the surface of, various cells. Humanised agonistic anti-CD28 monoclonal antibody is an antibody that is thought to bind a specific type of cells of the immune system called T lymphocytes. By binding these cells, it is thought that the antibody can stimulate them to attack and kill the cancer cells.

[Ref]

Which isn't anti-inflammatories (although that might be an effect) but immunotherapy. Parexel describe it as "being developed by sponsor TeGenero AG for the treatment of autoimmune/inflammatory diseases and hemato-oncological malignancies". TeGenero (an immunotherapeutics specialist) describes the drug as being developed for the treatment of immunological diseases with a high unmet medical need, such as multiple sclerosis, rheumatoid arthritis and certain cancers.

Well. I routinely get excited about news stories about this sort of stuff, and here it is, gone horribly wrong.

Still, in my usual "speak, then act" way, I've just put my name down for some TB research. Money's rubbish, though.

Sorry, that was all a bit grim, wasn't it? Have a stupid webshop: Customers who bought this also bought: moldy bread.

Comments

( 11 worms — Feed the birds )
juggzy
16th Mar, 2006 18:51 (UTC)
Oh, I was just posting about that. It's absolutely horrifying.
benchilada
16th Mar, 2006 18:52 (UTC)
Look, not all of us 'Muricans are all about makin' things more dangerouser.

Some of us feel that the use of a few nukular weaponz would make things EVEN MORE LESS DANGEROUSER.
cleanskies
16th Mar, 2006 20:20 (UTC)
ohhhh
sorry, should've said what I edited it too xx
tenderhooligan
16th Mar, 2006 19:02 (UTC)
Is that the former 'heroin' chruch at the bottom of Leopold street? Brutal.

That's about the thrid person to die on that corner in about a year - and I think there's been one near-fatal stabbing there recently too.
jackfirecat
16th Mar, 2006 20:40 (UTC)
a grave yard in many ways
crazycrone
16th Mar, 2006 20:45 (UTC)
Bad Sad World
I rang St Thomas' a couple of weeks ago trying to get on a trial,in search of Serbia money, but they wouldn't take me 'cos I take regular medication. Whew...
I keep thinking about the guy who'd had the placebo, and all of a sudden everyone started tearing their clothes off, and collapsing with exploded heads and stuff. He must have thought he was hallucinating. Brrrrr.
smallbeasts
16th Mar, 2006 22:00 (UTC)
lab rats (from Jo)
I also spotted it wasn't an anti-inflammatory, but a treatment for inflammatory diseases. I've been annoyed at the BBC over this. They really need to employ a scientist to check facts.

I'll translate "immunomodulatory humanized agonistic anti-CD28 monoclonal antibody" for you. Basically it's an antibody. "Monoclonal" means that it is a pure (there is only one type of antibody in the preparation). CD-28 is a substance on the surface of certain types of immune system cells, known as "T" cells. "anti" means that the antibody binds to CD28. Agonist means that when the antibody binds to the CD28, it causes the CD28 to respond, altering the function of the T cell. "Humanized" means that the antibody looks like a human antibody and "immunomodulatory", tells you that when the antibody binds to the CD28 it effects the immune system (obviously!).

So what were they trying to do with this drug? Well it appears that when T cells become cancerous they display many signals to say that they are sick. This should trigger other cells in the immune system to come along and kill them, getting rid of the leukemia. However this process is not very efficient. Scientists have found that they can make it much more efficient by binding antibodies to the sick cells, which is what they were trying to do here. My understanding is that this approach isn't altogether novel, and they have had limited success with antibodies binding to other cell surface substances.

So my initial guess, is that something went dreadfully wrong with the formulation (rather than the drug itself). Either that or this antibody reacts to things other than CD-28.....

In any case, it's pretty tragic.
cleanskies
17th Mar, 2006 10:48 (UTC)
Re: lab rats (from Jo)
thanks for the explaination, I was hoping you would
smallbeasts
17th Mar, 2006 18:56 (UTC)
Re: lab rats (from Jo)
No problem. Even tonight the BBC's explanation is quite poor.

By the way, could you recommend a free drawing program that Ellie could use? MS Paint doesn't quite do the job.
(Anonymous)
18th Mar, 2006 15:42 (UTC)
Re: lab rats (from Jo)
Smallbeast.....
Thanks for the info. I do have a question-is the T cell you mentioned the ones that AIDS attacks or an I out of my depth? Did you ever get a response on your MS Paint question?

Thanks
Bigun1_6605
(Anonymous)
18th Mar, 2006 15:35 (UTC)
Excellent explanation above. Monoclonal antibodies (Rituxan (http://www.gene.com/gene/products/information/oncology/rituxan/index.jsp)), in conjunction with standard chemotherapy, have been used with great success in prolonging the lives of people with cancer for about the past decade in the US (and probably the UK but not certain how much in use there).

The goal in cancer treatment is to limit the death of normal, healthy cells while targeting the cancerous ones which is difficult in diffuse cancers such as lymphoma as these cells, unlike a target specific tumor where radiation and chemo can be effective, are everywhere. Newest on the research horizon is radioimmunotherapy (RIT (http://www.leukemia-lymphoma.org/attachments/National/br_1098118596.pdf#search=%27Radioimmunotherapy%27)) which will combine these antibodies and target radiation to the specific cancer cell.

When you first posted this, before looking at the link, I actually thought you really were talking about lab rats, not humans. Monoclonal antibodies are known for fatal reactions so if this new antibody was not tested on animals (I cannot imagine) then that is purely criminal. Thanks for posting this--I've just e-mailed this to my fellow colleagues as these research companies don't always make their findings immediately known.
( 11 worms — Feed the birds )