Scientists harness immune system to prevent lymphoma relapse

The University of Manchester researchers, who were funded by the charities Leukaemia & Lymphoma Research and Cancer Research UK, have shown that, when used in conjunction with radiotherapy, the new drug is potentially four times more likely to lead to long-term survival than radiotherapy alone.

Relapse is a common fate for many lymphoma patients and new treatments are desperately needed. The new research, which is published online in Blood, the Journal of the American Society of Hematology (ASH), shows that the chemical R848 can be used to prime the immune system to fight cancer.

R848 is a chemical which signals to certain molecules known as receptors found on the surface of immune cells, triggering them into action. Receptors play a key role in the function of the immune cell by recognising harmful agents and instructing the cell to respond. It was shown that injections of R848 can generate a rapid expansion of specific anti-lymphoma immune cells known as 'killer T cells'.

Dr Simon Dovedi, of The University of Manchester's Institute of Cancer Sciences and the Manchester Cancer Research Centre, who conducted the research in the Targeted Therapy Group led by Professor Tim Illidge, said: "Excitingly we think that this new approach to treating cancer could be capable of giving patients a better response to conventional therapies through the generation of a lymphoma-specific immune response against tumour cells. This could be the key to ensuring long-term survival in more patients and reducing the number of relapses after initial therapy."

The Manchester team tested injections of R848, in combination with radiotherapy, in the laboratory on mice with lymphoma. It was found to have few side effects, with 100% of mice achieving long-term survival compared to just 28% of those mice which were treated with radiotherapy alone. In those mice that achieved long-term survival through treatment with R848 and radiotherapy, any re-introduction of cancer was completely rejected by the immune system in 75% of cases. These successful laboratory results mean that it could soon be used in early phase clinical trials for patients with lymphoma.

Professor Chris Bunce, Research Director of Leukaemia & Lymphoma Research, said: "While it is still early and this treatment has not yet been tested in humans, these results are hugely promising. One of the major obstacles to long-term successful treatment for many types of lymphoma has been relapse after initial successful treatment. Treatment with R848 can prime T cells to recognise various tumour-associated antigens, protecting patients from the return of the cancer."

Dr Kat Arney, Science Information Manager at Cancer Research UK, said: "Finding new ways to tackle lymphoma that has come back after treatment is vital if we're to beat this disease for good. Research is our best weapon against cancer, and we hope that this promising lab work will lead to more effective treatments for patients in the future."

The report is published online in the journal Blood, the Journal of the American Society of Hematology (ASH), under the title "Systemic delivery of a TLR7 agonist in combination with radiation primes durable anti-tumor immune responses in mouse models of lymphoma." Principal authors: Dr Simon Dovedi, Dr Jamie Honeychurch and Professor Tim Illidge of The Institute of Cancer Sciences, Manchester Academic Health Science Centre, University of Manchester