Scientists have discovered a
protein that plays a central role in promoting immunity to viruses
and cancer, opening the door to new therapies.
Experiments in mice and human cells
have shown that the protein promotes the proliferation of cytotoxic
T cells, which kill cancer cells and cells infected with viruses.
The discovery was unexpected because the new protein had no known
function and doesn't resemble any other protein.
Researchers from Imperial College
London who led the study are now developing a gene therapy designed
to boost the infection-fighting cells, and hope to begin human
trials in three years.
Cytotoxic T cells are an important
component of the immune system, but when faced with serious
infections or advanced cancer, they are often unable to proliferate
in large enough quantities to fight the disease.
By screening mice with genetic
mutations, the Imperial team discovered a strain of mice that
produced 10 times as many cytotoxic T cells when infected with a
virus compared with normal mice. These mice suppressed the
infection more effectively, and were more resistant to cancer. They
also produced more of a second type of T cells, memory cells,
enabling them to recognise infections they have encountered
previously and launch a rapid response.
The mice with enhanced immunity
produced high levels of a hitherto unknown protein, which the
researchers named lymphocyte expansion molecule, or LEM. They went
on to show that LEM modulates the proliferation of human T cells as
well as in mice.
The researchers now aim to develop
a gene therapy designed to improve immunity by boosting the
production of LEM. With the support of Imperial Innovations, the
technology commercialisation company for the College, the
researchers have filed two patents. A company called ImmunarT has
been formed with the aim of commercialising the technology.
Professor Philip Ashton-Rickardt
from Imperial, who led the study, said: "Cancer cells have ways to
suppress T cell activity, helping them to escape the immune system.
Genetically engineering T cells to augment their ability to fight
cancer has been a goal for some time and techniques for modifying
them already exist. By introducing an active version of the LEM
gene into the T cells of cancer patients, we hope we can provide a
robust treatment for patients.
"Next we will test the therapy in
mice, make sure it is safe and see if it can be combined with other
therapies. If all goes well, we hope to be ready to carry out human
trials in about three years."
Dr Claudio Mauro, who led the
research for Queen Mary University of London's William Harvey
Research Institute, said: "This study has identified the novel
protein LEM and unlocked an unexpected way of enhancing the ability
of our immune system to fight viruses or cancers. This is based on
the ability of the protein LEM to regulate specific energy
circuits, and particularly mitochondrial respiration, in a subset
of white blood cells known as cytotoxic T cells.
"This discovery has immediate
consequences for the delivery of innovative therapeutic approaches
to cancer. Its ramifications, however, are far greater as they can
help explaining the biological mechanisms of widespread human
diseases involving altered immune and inflammatory responses. These
include chronic inflammatory and autoimmune disorders, such as
atherosclerosis and rheumatoid arthritis."
The
paper, The protein LEM promotes CD8+ T cell immunity through effects
on mitochondrial
respiration,is published
in Science.