A little more on OX40/influenza from this month's Scientist
the-scientist.com
FIGHT THE FLU, IGNORE THE BUG
At the start of this year's particularly worrisome flu season, researchers at London Imperial College in the United Kingdom posed a comforting thought: Suppose the bug's nasty symptoms could be avoided without vaccination or antiviral drugs by targeting the immune responses responsible for influenza's misery. Their tests on mice showed positive results, they say. Maybe so, say the skeptics, but that doesn't prove how humans would respond.
The Imperial College researchers have found that a receptor molecule called OX40 is overexpressed in T cells responding to a viral infection, but not in the remaining T-cell population.1 The receptor can be blocked using an OX40-immunoglobulin fusion protein called OX40:Ig. This, the researchers say, should temper overzealous immune responses in the lungs.
Tracy Hussell and colleagues, who tested the drug on mice injected with influenza type A, found that clinical symptoms such as congestion and high body temperature were virtually eliminated. Hussell says there's no reason why the treatment could not be extended to humans, after symptoms have emerged. "Mice could show signs of illness for three days, and as soon as you administer this reagent, it stops clinical symptoms in their tracks."
In the future, humans could experience similar remission of symptoms, according to Alan Hay, director of the WHO Collaborating Centre for Reference and Research on Influenza at the UK National Institute for Medical Research. "It's interesting work, but it's early stages and needs further development," says Hay.
Brad Magor, assistant professor, Department of Biological Sciences (Immunogenetics), University of Alberta, is more dubious. "Mice are not natural hosts to influenza A, so their response to the pathogen is less likely to reflect that of a natural host such as a chicken, swine, or human." Magor says he's concerned that the body might permanently lose influenza-specific memory cells as a result of the treatment. He conceded, however, that blocking OX40 molecules showed significant promise for modulating immunity and inducing tolerance to engrafted organs.
Hussell says the group is focusing on the influenza treatment for now and is applying to the UK Medical Research Council and the Wellcome Trust for funding to begin human clinical trials. The Imperial College group collaborates with Xenova, a UK-based biotech that explores various therapeutic uses of OX40, including autoimmune disease and cancer.
--Philip Hunter
1. I.R. Humphreys et al., "A critical role for OX40 in T cell-mediated immunopathology during lung viral infection," J Exp Med, 198:1237-42, Oct. 20, 2003. |
