New drug testing method could reduce need for animal testing
12 March 2012
Scientists from the University of Southampton are to develop a
laboratory-based system to accurately predict immune responses to drugs
based on bio-active proteins.
These systems, called assays, would be used to pre-screen candidate
drugs and reduce the need for testing on animals.
It is hoped that the assays will help avoid incidents such as the
TGN1412 trials in London six years ago, which saw six healthy
volunteers experience severe adverse reactions to a clinical drug
that had been tested on animals with no effects.
Martin Glennie, Professor of Immunochemistry and Head of Cancer
Sciences at the University, says: “Animal testing remains the
industry standard for predicting patient toxicity but it can
underestimate or even miss the levels of toxicity observed in the
first-in-human trials, as we saw with the TGN1412 trials in 2006.
Predicting toxicity using in vitro human assays would reduce the
risk of incidents like this and also refine pre-clinical animal
The study is funded by the National Centre for the Replacement,
Refinement and Reduction of Animals in Research (NC3Rs) under its
CRACK IT scheme, a ground-breaking open innovation programme to fund
projects that accelerate the application of the 3Rs.
Professor Glennie, together with Dr Tony Williams, Reader in
Clinical Immunology and Allergy at the University of Southampton,
will work with a team of researchers, which includes Dr Mark Coles
of the Centre for Immunology and Infection at the University of
York, to test a range of drugs called monoclonal antibodies to see
if they can find a way of predicting their toxicity in patients.
It is known that most of the toxicity seen when using monoclonal
antibodies comes from blood cells called lymphocytes. When these
cells become activated patients feel ill, with symptoms ranging from
a mild cold, to life-threatening swelling of vital organs. These
activated lymphocytes make important ‘messenger’ molecules called
cytokines and it is these messengers which cause the toxicity during
a so-called ‘cytokine storm’.
Drug testing in animals does not always predict how a monoclonal
antibody will behave in patients. Southampton scientists will
develop laboratory-based tests that will reliably predict cytokine
release when a monoclonal antibody is given to patients.
“Worldwide more than 30 monoclonal antibodies, such as Herceptin
and Remicade, have now been approved for human use, and they are
rapidly changing the way we control and treat diseases ranging from
cancer to rheumatoid arthritis,” adds Professor Glennie.
“The success of this class of drugs is such that hundreds more
are under development. We have a long and distinguished history of
making and using monoclonal antibodies in Southampton and so we feel
ideally placed to undertake this important research and hopefully
reduce the need for pre-clinical testing in animals.”