Help wanted: No immune experience required

From the news release:

"Around 50% of adult human T cells are memory cells, having been activated by infections and illnesses during the course of a person's life. However, animal models, such as those used to test TGN1412 before tests were carried out on humans, do not have many memory T cells because they are deliberately kept in a sterile environment where they are shielded from infections."

Hmmm. Presumably all the specific pathogen free (SPF) colonies are part of a plan to eliminate pesky diseases that vivisectors view as confounding variables. Oh. You mean immune systems don't exist in a vacuum? And that species differences and experience influence immune function? Well go figure. (shucks)

"The research, by scientists from Imperial College London, King's College London, and the Babraham Institute, is presented today at the Club de la Transplantation conference in Cernay la Ville, near Paris.

Dr Federica Marelli-Berg, lead author of the research from the Department of Immunology at Imperial College London, explained: "The drug TGN1412 appeared to be relatively safe when it was tested in animal models. However, when the drug was tested on human volunteers, some experienced very severe side-effects."

I'm sorry. Did she say that some volunteers had very severe side effects? How would anyone in her right mind not admit that all six men suffered extraordinary, indeed life-threatening, effects?

"TGN1412 was developed to treat chronic inflammatory conditions, including rheumatoid arthritis, leukaemia and multiple sclerosis, which are caused by the body's immune system attacking itself. It was thought that by targeting CD28, the drug could over-stimulate the rogue T cells, making them burn out and die."

Doh!

Not everyone is so quick to buy this spiel. One expert consulted by the science journal Nature had a very different view:

As part of a report into how to minimize the risks of future clinical trials, immunologist Stephen Inglis of the National Institute for Biological Standards and Control in London developed a new test, using human cells in a test tube, that could have spotted the risk of a cytokine storm (see 'New test could weed out dangerous drug trials').

Inglis also doubts that Marelli-Berg's theory represents the whole story. Monkey cells did not respond to his test in the same way, suggesting that there is something fundamentally different about the two species' cells, rather than simply a question of which cells are present.

What's more, he says it is unclear whether or not lab monkeys do indeed have less-developed immune systems. "They're not like mice," he says. "Colonies of monkeys live in groups, they're not in individual cages, they do get infections and they're not pristine. We would now recommend using human cells for preclinical trials. But whether that is the cause is a different thing."

Maybe monkeys used in preclinical trials conducted in European labs live in groups. Those here in the US certainly do not.
Other posts on TGN1412 can be found in the pharma category at right.

Original news item: Researchers propose reason for severe side-effects of Northwick Park clinical trial