Richard Baugh was awarded a Brain Research UK PhD studentship in 2017 to enable him to pursue research into the brain tumour glioblastoma.
His research was focused on developing new immunotherapies for the treatment of glioblastoma. He worked under the supervision and guidance of Professor Leonard Seymour, a leader in the field of oncolytic virotherapy.
Following completion of an ambitious programme of work, Richard was awarded his DPhil from the University of Oxford in summer 2022.
Glioblastoma (GBM) is a tumour that grows and spreads quickly and is hard to treat.
It is the most common primary brain tumour in adults, with around 2,500 cases diagnosed every year in the UK.
For those affected, the prognosis is bleak. The tumours are difficult to remove surgically because they have finger-like tentacles that can wrap around vital brain structures. Following surgery to remove the bulk of the tumour, radiation and chemotherapy are used to slow the growth of remaining tumour. But glioblastomas are aggressive tumours and often appear resistant to treatment or quickly recur.
Only 20 per cent of glioblastoma patients survive more than one year from diagnosis, and only three per cent survive more than three years.
A crucial feature of our immune system is its ability to differentiate between the body’s own cells and ‘foreign’ cells. This enables it to attack the foreign cells while leaving normal cells alone.
However the immune system does not recognise cancerous cells as foreign, meaning that they evade immune surveillance and are able to grow and spread.
There are a number of different immunotherapy approaches, all based on the premise of flagging the tumour as ‘foreign’ so that an immune response is triggered.
Oncolytic virotherapy involves the use of engineered viruses that can selectively infect and destroy cancer cells. Not only do the viruses directly destroy the tumour cells, but they also stimulate an immune response, so that the body’s natural defences are roused and sweep in to destroy any remaining tumour.
Richard worked with a form of oncolytic herpes simplex virus (oHSV), called G207, which had been previously trialled in GBM. Although promising results had previously been achieved in the laboratory, clinical trial results were disappointing.
Richard worked to enhance the effects of G207 by using it as a vector to deliver gene therapy directly to the cancer cells, to flag them to the immune system and enhance the immune response.
His work revealed a potential strategy for augmenting the activity of the virus to further kill GBM cells and provoke an immune response in the tumour microenvironment. One of the main limitations of oHSV therapy for GBM, as well as of conventional therapies, are sub-populations of resistant glioblastoma stem cells (GSCs), which contribute towards resistance and recurrence. G207 has previously been shown to be ineffective against these GSCs but Richard has demonstrated that the molecule produced by their gene therapy is able to target the GSCs. Arming G207 in this way in future clinical trials could therefore hold the key to eliminating these stubborn cells.
Given the dismal prognosis for those diagnosed with glioblastoma, and the lack of progress over recent decades, there is a real and pressing need for new treatments.
Richard’s research offers hope of an important new tool that could form the basis of new treatments for glioblastoma.
Richard has benefited hugely from this training opportunity and has used it to drive forward several promising new approaches to GBM therapy.
Throughout the project, Richard has shown an enthusiasm and ability to drive the project forward with a distinct GBM focus, always aiming to use the best scientific options for ultimate patient benefit. He has produced an excellent thesis, several good publications and established new approaches for treatment of GBM.
- Professor Leonard Seymour
Dyer, A, Baugh, R, Chia, SL et al. Turning cold tumours hot: oncolytic virotherapy gets up close and personal with other therapeutics at the 11th Oncolytic Virus Conference. Cancer Gene Ther 26, 59–73 (2019). https://doi.org/10.1038/s41417-018-0042-1
Baugh, R, Khalique, H, & Seymour, LW. (2020). Convergent Evolution by Cancer and Viruses in Evading theNKG2D Immune Response. Cancers, 12(12), 3827. https://doi.org/10.3390/cancers12123827
Pokrovska, TD, Jacobus, EJ, Puliyadi, R, Prevo, R, Frost, S, Dyer, A, Baugh, R, Rodriguez-Berriguete, G, Fisher, K, Granata, G, Herbert, K, Taverner, WK, Champion, BR, Higgins, GS, Seymour, LW, & Lei-Rossmann, J. (2020). External Beam Radiation Therapy and Enadenotucirev: Inhibition of the DDR and Mechanisms of Radiation-Mediated Virus Increase. Cancers, 12(4), 798. https://doi.org/10.3390/cancers12040798
Khalique H, Baugh R, Dyer A,et al. Oncolytic herpesvirus expressing PD-L1 BiTE for cancer therapy: exploiting tumor immune suppression as an opportunity for targeted immunotherapy. Journal for Immunotherapy of Cancer. 2021 Mar;9(4): e001292. https://doi.org/10.1136/jitc-2020-001292
Richard T Baugh, Hena Khalique, Janet Lei-Rossmann, Len Seymour; Abstract P024: Using innate immune ligands to activate adaptive immune cells for glioblastoma therapy. Cancer Immunol Res 1 January 2022; 10 (1_Supplement): P024. https://doi.org/10.1158/2326-6074.TUMIMM21-P024
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