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UK-Förderung (523.555 £): CANCER THERAPY USING ANTIBODY-MEDIATED DELIVERY OF ONCOLYTIC VIRUSES Ukri01.03.2019 Forschung und Innovation im Vereinigten Königreich, Großbritannien

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CANCER THERAPY USING ANTIBODY-MEDIATED DELIVERY OF ONCOLYTIC VIRUSES

Zusammenfassung Some viruses that infect humans are currently under investigation for the treatment of cancer; these are referred to as oncolytic viruses. Some of these oncolytic viruses rarely produce serious symptoms in humans while others have been modified so that they no longer cause disease. They act both by directly killing cancer cells and also by stimulating the body's own immune system to attack the cancer. However, with regard to oncolytic viruses, the immune system represents a double-edged sword, because as well as stimulating anti-cancer immune responses, oncolytic viruses also stimulate anti-viral immune responses, including the production of anti-viral neutralizing antibodies. The current perception is that these anti-viral neutralizing antibodies are a barrier to intravenous delivery of oncolytic viruses, because they will neutralize the virus and prevent it reaching the tumour. Thus repeated intravenous injections would be ineffective because of the anti-viral immune response that is generated after the first dose is given to a patient. However, our research has unexpectedly found that neutralizing antibodies may play a role in cancer treatment. We have found that some immune cells in the blood called monocytes can be loaded with pre-formed virus-antibody complexes (so the virus is fully neutralized) and then, by mechanisms not currently known, reactivate the virus so that it can be transferred to tumour cells which it infects and kills. This is very unexpected, as monocytes are thought to destroy all antibody-coated virus they encounter. Our research therefore has significant implications for the future of oncolytic virotherapy and for the design of clinical oncolytic virotherapy treatment strategies. We propose to investigate this further to determine how many of the oncolytic viruses currently under investigation in the clinic, can be reactivated by monocytes in this way. We will also find out whether other cells in the blood can also reactivate antibody-neutralized viruses in the same way as monocytes and investigate the mechanisms involved in the process. This work will increase our understanding of the role of neutralizing antibodies in oncolytic virotherapy and enable improvements in the use of oncolytic viruses for treating cancer.
Kategorie Research Grant
Referenz MR/S008578/1
Status Closed
Laufzeit von 01.03.2019
Laufzeit bis 31.12.2024
Fördersumme 523.555,00 £
Quelle https://gtr.ukri.org/projects?ref=MR%2FS008578%2F1

Beteiligte Organisationen

University of Leeds
Institute of Cancer Research
Amsterdam UMC
Mayo Clinic and Foundation (Rochester)

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