Therapeutics


Bringing IO together: how an immunologist and oncologist collaborate in an emerging field


For many years, immunology and oncology operated as separate disciplines within drug discovery. However, recent advances in immuno-oncology (IO) have demonstrated what can be achieved when the two disciplines join forces in developing novel treatments for patients. From checkpoint inhibitors to CAR-T cells and model selection designed to reflect more personalised medicine approaches, immuno-oncology is shifting how both immunologists and oncologists approach drug discovery and development.


I


n a Q&A, Dr Julia Schüler, DVM, Research Director at Charles River, which specialises in oncology, and Dr Louise Brackenbury, Principal


Scientist for Cell Biology at Charles River’s newly- acquired KWS BioTest, which specialises in immunology, will provide their unique perspectives on the ways in which IO is reshaping the industry.


What made you realise that IO was going to have a major impact on your field? Louise Brackenbury (LB): There has been plenty of evidence over the years indicating an important role for the immune system in controlling cancer, however the difficulty had been finding tractable targets. For example, in a 2006 report, Galon and colleagues demonstrated that the density and loca- tion of tumour-infiltrating CD3+ and CD45RO+ were a better indicator of patient survival than classical methods1. What really changed everything was when the


first few data sets from early clinical trials started to appear, showing the incredible results with Ipilimumab2 alone and in combination with


Drug Discovery World Spring 2018


Nivolumab3. It immediately became clear that enor- mous progress had been made, and that our ability to manipulate the immune system has provided us with a powerful tool to fight even late-stage and chemotherapy or radiation-resistant cancers.


Julia Schüler (JS): The complicated cross-talk between cancer cells and the tumour microenviron- ment (TME) with its different compartments was a research focus in tumour biology for decades. Nevertheless, identifying druggable targets in the TME remained challenging. Science Magazine’s ‘Breakthrough of the Year’ in 2013 summarised the impressive results achieved in clinical trials with checkpoint inhibitors, first in late-stage melanoma. For the first time, specifically targeting a non-tumour cell led to significant tumour cell killing across different indications, independent of staging and treatment history.


What surprised you when you started to conduct IO studies? LB: Coming from an autoimmune/inflammatory background, I had to get used to the idea that


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By Dr Julia Schüler and Dr Louise Brackenbury


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