The UK and Dutch researchers developed a rapid DNA sequencing technology that newly identified 21 different molecules, called T cell receptors (TCRs), that can recognise markers found in cells from 11 different subsets of cancer.
White blood cells known as killer T cells are the assassins of the immune system and it is their job to seek out and destroy infected cells. They can also potentially kill cancer cells but often fail to do so, partly because our immune system is programmed not to attack our own bodies. Since cancer cells are formerly healthy cells that are growing out of control, T cells normally do not recognise them as a threat.
Treatment called ‘immunotherapy’ works by taking a sample of T cells from the blood of a cancer patient and inserting TCR genes that recognise specific markers, or ‘antigens’, carried by cancer cells. When these modified T cells are reintroduced into to the patient, the T cells can hunt down and kill cancer cells, while sparing healthy cells. This approach has already been tested in patients with a variety of cancers, including blood cancers and skin cancers, with very promising results.
Unfortunately, antigens found on patients’ cancer cells vary considerably and if the engineered T cells are not matched exactly to recognise each cancer subset, then the immunotherapy will not be effective.
Dr Gavin Bendle, now based at the University of Birmingham, was funded by Leukaemia & Lymphoma Research to carry out the research with Dr Carsten Linnemann and Prof Ton Schumacher at The Netherlands Cancer Institute. He said, “To be able to treat large numbers of patients with different types of cancer, large collections of TCRs specific to each cancer subset are needed. The DNA scanning technology that we have developed enabled us to rapidly assemble a library of TCRs that have the potential to be used to treat many cancer types and subtypes.”
The research is published online in the journal Nature Medicine.
Professor Chris Bunce, Research Director of Leukaemia & Lymphoma Research, said, “For the past decade, immunotherapy has been seen by some as the holy grail of targeted cancer treatment, especially for those patients who cannot be cured with standard chemotherapy drugs. It has had very promising results in patients with a variety of cancers but it does not work in all cases and can be laborious to produce. This study is a highly significant step forward in individualising immunotherapy in a rapid way, making it a potential cure for more cancer patients than ever before.”
Dr Bendle, now based at the School of Cancer Sciences at the University of Birmingham, is currently running a five-year study, also funded by Leukaemia & Lymphoma Research, to refine which TCRs from the library are best suited to treating patients with myeloma, an as-yet incurable type of blood cancer. These TCRs will then be tested in clinical trials for myeloma patients.
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Notes to editors
The findings are published online in the journal Nature Medicine on 13 October under the title ‘High-throughput identification of antigen-specific TCRs by TCR gene capture’. Corresponding authors: Dr Gavin Bendle & Prof Ton Schumacher, Department of Immunology, The Netherlands Cancer Institute
About Leukaemia & Lymphoma Research
Leukaemia & Lymphoma Research is the only UK charity dedicated to improving the lives of patients with all types of blood cancer, including leukaemia, lymphoma and myeloma. Its life-saving research is focused on finding causes, improving diagnosis and treatments, and running ground-breaking clinical trials for all blood cancer patients. Around 30,000 people of all ages, from children to adults, are diagnosed with blood cancers such as leukaemia, lymphoma and myeloma every year in the UK.