Anticancer Viruses and Cancer Vaccines
Our research develops anti-cancer viruses that are able to infect and kill cancer cells, while leaving normal cells unharmed. This approach exploits the natural life cycle of the virus, which lyses infected cells in order to release progeny virus particles, allowing the infection to spread from cell to cell through the tumour. The life cycle of some viruses, such as adenoviruses, is intimately dependent on the activities of the cells they infect, and this provides a range of opportunities to engineer viruses that are only active when they encounter the specific environment of a tumour cell.
Adenoviruses can be designed that are dependent on deregulated cell cycle, dysfunctional apoptosis pathways, enhanced glycolytic metabolism and many others. In this way the virus amplifies itself within the tumour, reaching high local concentrations and potentially infecting all tumour cells. In addition this 'oncolytic' type of cell killing is very inflammatory, providing the possibility to create an anti-cancer immune response. These agents are often known as ‘oncolytic vaccines’.
Finally our viruses can be 'armed' to encode additional therapeutic agents, to be expressed only within the tumour; this provides a simple and versatile approach to targeted cancer therapy using a range of potent biological agents. For example encoding bispecific T cell engagers (BiTEs) can repurpose T cells within tumours to attack cells bearing any chosen antigen. Alternatively agents can be encoded to promote antigen-agnostic antigen cross presentation, important for systemic cancer vaccines, or to reverse the immune-suppressive functions of the tumour stroma.
The group has led to formation of various spinout companies and startups, including Psioxus Therapeutics, Macrophox, Theolytics, Native Antigen Company and Oxford Genetics. Each of these companies seeks to develop advanced technologies for improved human healthcare, and several company-sponsored clinical trials have been held in both the USA and Europe, alongside a handful of university-sponsored studies. In this way we seek to maximise the impact of our research, leveraging commercial funding sources for faster and more advanced development.
Kerry Fisher - Associate Professor of Translational Research
Hena Khalique - Postdoctoral Researcher
Ahmet Hazini - Postdoctoral Researcher
Richard Baugh - Postdoctoral Researcher and Laboratory Manager
Flurin Caviezel - DPhil Student
Arthur Dyer - Laboratory Manager
Mahnoor Nadeem - DPhil Student
Weiheng Su - DPhil Student
Peter Wan - DPhil Student
Henry Brigden - DPhil Student
Emma Paige - DPhil Student
Kate Friesen - DPhil student
Fernando Gallardo - DPhil Student
- Dyer A, Schoeps B, Frost S, Jakeman P, Scott EM, Freedman J, et al. (2019) Antagonism of Glycolysis and Reductive Carboxylation of Glutamine Potentiates Activity of Oncolytic Adenoviruses in Cancer Cells, Cancer Research, 79(2), pp. 331-45.
- Freedman JD, Duffy MR, Lei-Rossmann J, Muntzer A, Scott EM, Hagel J, et al. (2018) An Oncolytic Virus Expressing a T-cell Engager Simultaneously Targets Cancer and Immunosuppressive Stromal Cells, Cancer Research, 78(24), pp. 6852-65.
- Freedman J.D., Hagel J., Scott E.M., Psallidas I., Gupta A., Spiers L., et al. (2017) Oncolytic adenovirus expressing bispecific antibody targets T-cell cytotoxicity in cancer biopsies. EMBO Molecular Medicine, 9(8), pp. 1067-87.
- Garcia-Carbonero R., Salazar R., Duran I., Osman-Garcia I., Paz-Ares L., Bozada J.M., et al. (2017) Phase 1 study of intravenous administration of the chimeric adenovirus enadenotucirev in patients undergoing primary tumor resection. Journal of ImmunoTherapy of Cancer, 5(1):71.
- Hazini A., Fisher K. & Seymour L. (2021) Deregulation of HLA-I in cancer and its central importance for immunotherapy. Journal of ImmunoTherapy of Cancer, 9(8).
- Khalique H., Baugh R., Dyer A., Scott E.M., Frost S., Larkin S. et al. (2021) Oncolytic herpesvirus expressing PD-L1 BiTE for cancer therapy: exploiting tumor immune suppression as an opportunity for targeted immunotherapy. Journal of Immunotherapy Cancer, 9(4).
- Lynn G.M., Chytil P., Francica J.R., Lagova A., Kueberuwa G., Ishizuka A.S., et al. (2019) Impact of Polymer-TLR-7/8 Agonist (Adjuvant) Morphology on the Potency and Mechanism of CD8 T Cell Induction, Biomacromolecules, 20(2), pp. 854-70.
- Lynn G.M., Sedlik C., Baharom F., Zhu Y., Ramirez-Valdez R.A., Coble V.L., et al. (2020) Peptide-TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens. Nature Biotechnology, 38(3), pp. 320-32.
- Scott E.M., Jacobus E.J., Lyons B., Frost S., Freedman J.D., Dyer A., et al. (2019) Bi- and tri-valent T cell engagers deplete tumour-associated macrophages in cancer patient samples, Journal of ImmunoTherapy of Cancer, 7(1), 320.
- Su W., Patricio M.I., Duffy M.R., Krakowiak J.M., Seymour L.W., & Cawood R. (2022) Self-attenuating adenovirus enables production of recombinant adeno-associated virus for high manufacturing yield without contamination, Nature Communications, 13(1); 1182.