Scientists at Censo Biotechnologies in collaboration with the Leeds Institute of Cancer and Pathology, at the University of Leeds are developing a new approach to cancer research using stem cell technology
Neural progenitor cells (NPC) derived from High Grade Glioma iPSCs. NPCs express high levels of the neural stem cell protein Nestin (Green) and the transcription factor FoxG1 (Red). Copyright Censo Biotechnologies Ltd 2017.
Censo will create induced pluripotent stem cells (iPSCs) from brain tumours removed from patients as part of their clinical treatment.
The stem cells will be used in the project to identify drugs, which could prevent or limit the growth of brain cancer cells.
Co-funded by the UK’s innovation agency, Innovate UK, the 2 year project is one of the first major programmes to create iPSCs from cancer tissue. Cancer Research Technology will support the drug discovery phase of the project, providing guidance, and helping identify and source ways to test prospective drugs.
The researchers will focus on the most aggressive type of brain tumour, high-grade glioma (HGG).
These tumours are extremely difficult to treat and even with the best treatment available today, the typical patient with HGG will only survive on average 12–15 months after diagnosis.
Until now, it has not been possible to investigate the earliest stages of the development of these tumours, which occur before the patient is diagnosed.
At Leeds, the Stem Cells and Brain Tumour Group, led by Dr Heiko Wurdak, has worked with Mr Ryan Mathew from the Department of Neurosurgery to use iPSC technology to study the cancer genome of HGG by reprogramming to the stem cell stage.
Dr Heiko Wurdak, Stem Cells and Brain Tumour Group, University of Leeds said: “It is challenging to develop better therapies for a cancer that entails more than one hundred tumour types, numerous clinical subtypes and a broad spectrum of patient-to-patient differences. We are very excited by the prospect of generating a considerable number of new brain cancer models, which we hope will represent many of the patient-to-patient differences observed in the clinic.
"This stem cell technology-based project will provide a near infinitive resource for studying how the patient-specific features of an aggressive tumour (such as the genetic information) influence the growth of tumour stem cells that are resistant to therapy. We hope that this new avenue towards drug discovery will help to further develop precision medicine for brain cancer providing improved options for the efficient treatment of aggressively growing tumours.”
First pioneered in 2006, iPSC technology makes it possible to create stem cells from almost any tissue sample, normally a person’s healthy tissue is used. In contrast, the Patient Derived iPSCs for High Grade Glioma project will use tumour cells as the starting material.
Researchers plan to use the newly generated tumour cells to better represent patient to patient differences in laboratory studies with the primary goal to find answers why the tumour cells fail to behave like healthy brain cells, and to identify tumour cell vulnerabilities that can be exploited for personalised cancer medicine.
A specific focus of the research will be to find drugs, which force brain tumour stem cells to develop into a more mature, less aggressive state and to investigate how cancer cells can change their characteristics to evade and survive conventional cancer treatments.
Aidan Courtney, CEO of Censo Biotechnologies, said: “Censo has established an unrivalled expertise amongst companies to create new iPSC lines from human tissue. We believe that patient derived iPSCs (PDi) will have a profound effect on the way that new drugs are developed and ultimately the way that clinicians determine the best treatment for a specific patient."
This is a ground breaking collaboration, which has the prospect of creating a new means of investigating how this cancer develops and why it is so aggressive.”
Censo Biotechnologies has extensive capacity to create and use iPSCs for drug discovery research with sites in Edinburgh and Cambridge, UK. The Company uses this capacity to produce stem cells from large diverse groups of individuals, so that drug development companies can understand how the efficacy of its drugs varies across the population. This underpins faster drug development and enables the right drug to be targeted to the right patient.
Dr Stuart Farrow, Director of Biology at Cancer Research Technology, said: “This exciting new approach could enable the discovery of potential new targeted treatments using tumour cells taken directly from patients and reprogrammed to grow in the lab.”
Drug discovery companies are increasingly recognising iPSC technology will allow them to test potential new drugs in the laboratory more effectively — reducing the risk of expensive failures in clinical trials.