Experiments in mice and human cells have shown this new protein promotes the growth of ‘cytotoxic T cells’, a type of white blood cell 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.
The study, published today in the journal Science, was led by Imperial College London in partnership with Queen Mary University of London, along with ETH Zurich and Harvard Medical School.
The team 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, advanced cancer or autoimmune diseases such as rheumatoid arthritis, they are often unable to grow in large enough quantities to fight the disease.
By screening mice with genetic mutations, the researchers 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 team found the mice with enhanced immunity produced high levels of a previously unknown protein, which the researchers named Lymphocyte Expansion Molecule, or LEM. They went on to show that LEM controls the growth of human T cells, as well as in mice, by effecting the process of mitochondrial respiration, which provides cells with the energy required for growth.
A spinout company called ImmunarT Ltd will develop gene therapy designed to improve immunity by boosting the production of LEM.
Dr Claudio Mauro, who led the research from the Centre for Biochemical Pharmacology, based within 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.”
Professor Philip Ashton-Rickardt from the Section of Immunobiology in the Department of Medicine at 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.”
The research was funded by the Medical Research Council, the Wellcome Trust and the British Heart Foundation.
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