Developing precision virotherapies with “molecular switches” for the treatment of diffuse midline glioma (DIPG).

Summary: Diffuse midline glioma (DIPG) is a rare yet devastating childhood cancer. It originates in the brainstem in the midline of the brain and is difficult to treat surgically. Standard of care is limited to radiotherapy. Most children do not survive for a year following diagnosis, only 10% survive two years and less than 2% survive for 5 years or more. New treatments are therefore desperately required.

The Viral ImmunoTherapies and Advanced therapeutics Laboratory (VITAL) develop “trained” viruses with significant advantages in treating cancer. These viruses are “tailored” genetically to selectively kill cancer cells, amplifying the therapy at the point of need (in the tumour) and stimulate an anti-cancer response. These viruses can be further altered to produce potent anti-cancer medicines at the tumour site – thus turning the tumour into a factory producing medicines to enable its own destruction.

The VITAL lab has a record in translating scientific breakthroughs to the clinic. We have already “trained” a virus which recognises a cancer specific marker called αvβ6 integrin, and first in human trials will commence in Q4 2024 (see https://www.accessiontherapeutics.com/trocept). Unfortunately, αvβ6 integrin is absent in gliomas, meaning such cancers are refractory to this agent. We have therefore engineered a new, glioma targeting “smart virus” that infects using an alternative marker present in glioma.

Whilst we have shown that our newly generated agent selectively infects glioma cells selectively through this marker, we aim to improve this agent further to address the presence of low levels of this receptor on healthy cells. By developing new molecular “tricks” we can improve the virus and ensure that the virus can only replicate and produce anticancer medicines in tumour cells. This project aims to firstly evaluate our agent specific DIPG cell lines and secondly the student will develop “molecular switches” which can be switched on in specific cell types (glioma). These will improve our smart viruses by restricting both replication and production of anticancer medicines to glioma cells.

Clinical impact: We have good experience of taking agents from bench to bedside with our “Trocept” technology and clinical collaborations to aid our translation to the clinic. We have gained momentum in this area, protected our IP, and developed a robust technology. We are confident that with a committed team and suitable funding, we can reach clinical trials by 2030. This position, if awarded, will be a significant part of this journey.

How to Apply  

This studentship has a start date of October 2024. In order to be considered you must submit a formal application via Cardiff University’s online application service.

There is a box at the top right of the page labelled ‘Apply’, please ensure you select the correct ‘Qualification’ (Doctor of Philosophy), the correct ‘Mode of Study’ (Full Time) and the correct ‘Start Date’ (October 2024). This will take you to the application portal. 

In order to be considered candidates must submit the following information: 

 • Supporting statement 

• CV 

• Qualification certificates 

• References x 2 

• Proof of English language (if applicable) 

International applicants are welcomed if the difference in fees can be covered.