Developments in Immuno-oncology
We aim to realise the long-term curative benefits of immunotherapy for more patients by devising new treatments, broadening the impact of existing treatments, and reducing side effects.
The importance of the immune system in cancer biology has long been understood. However, immuno-oncology - treatments that take advantage of the body's immune system to fight cancer – is only recently being applied in the clinic, whilst its full potential for benefiting patients is far from reached. Oxford’s immunology expertise is vast, most recently in the field of vaccine development for global pandemics - but it has also been crucial in enabling clinical success in the field of cancer research, such as:
- Discovery of regulatory T-cells and their role in intestinal homeostasis (Fiona Powrie)
- How tumours evade the immune response by tryptophan degradation and the development of therapeutic IDO inhibitors (Benoit Van den Eynde)
- Discovery of the first tumour-specific rejection antigens that have been integrated into the first generation of ChAdOx anti-cancer vaccines (Benoit Van den Eynde, Adrian Hill)
- The discovery of tumour necrosis factor alpha and development of the first immunotherapeutic antibody (Marc Feldmann)
- Discovery of the antigen processing pathway for cytotoxic T lymphocytes, and the mechanism of some of its component molecules (Alain Townsend, Vincenzo Cerundolo, Tim Elliott)
By coordinating research through this theme, Oxford Cancer seeks to revolutionise the use of immuno-oncology therapeutics in the clinic. Through the application of our leading expertise in fundamental immunology we will enable more patients, with a wide range of cancer types, to benefit safely from their tailored use.
In the last 15 years, the introduction of immuno-oncology into the clinic has transformed the life expectancy of patients with certain types of cancer (e.g. melanoma) from months, to decades. However, not all patients’ tumours respond to current immuno-oncology agents, most cancer types are totally insensitive to treatment, and in a very small number of patients the side effects are lethal.
By establishing new collaborations across technical disciplines and organisational boundaries, we seek to compare immune responses in healthy people, and patients with cancer or cancer-related conditions, in order to comprehensively understand the underlying immune mechanisms that influence cancer incidence and outcomes. With this knowledge we will be able to define the mechanisms by which cancers are able to evade the immune response during tumour development and treatment. This understanding will help us to the target the application of existing treatments, develop of new ones, and devise strategies to minimise harmful side-effects.
Oxford Cancer seeks to train scientists at scale with the technical, analytical and conceptual skill sets required to apply and integrate immunology to cancer research questions and export this expertise across the globe. Find out more about the challenges Oxford cancer researchers are addressing in this theme below.
What are the challenges we are tackling?
1. Expanding the immuno-oncology footprint
Immuno-oncology treatment is curative in many cases, however there are significant numbers of patients for which they are ineffective. Understanding why this is will allow us to better target these expensive agents to individuals most likely to benefit, as well as developing new strategies for sensitising unresponsive patients.
Oxford is uniquely placed to establish a common phenotyping platform and shared data repository to widen access to technologies and data for researchers with expertise in inflammation, cellular therapies, vaccines and viruses, infection, microbiome, adaptive immunity and novel immune-typing technology. By drawing these groups together we will be able to build a comprehensive understanding of the distinct phenotypic and functional states of the tumour immune microenvironment (TIME) and the immune mechanisms associated with successful therapy responses including conventional (chemo/radiotherapy) as well as immunotherapy.
We are overcoming barriers to developing a comprehensive analysis of the immunobiology of normal and diseased tissues by harmonising data across multiple organ-specific pathologies. This will pave the way for novel therapeutic strategies developed by our abundant clinical and translational expertise.
2. Minimising immuno-oncology toxicity
All cancer treatments have toxic side-effects. Understanding and predicting immune-related adverse side-effects is essential to minimise the morbidity associated with immuno-oncology treatment and improve patient care.
With expert researchers in the area of autoimmune conditions of the organs which are affected by immuno-oncology side effects (irAEs - including gut, skin, joints and liver), Oxford is uniquely placed to derive novel insights into the contributing factors that cause immune-toxicity. By comparing the different immune phenotypic stages of these conditions, their triggers will be identified so that we can develop new ways to predict and prevent them from happening. In doing so, we may also be able to improve the efficacy of the cancer treatment itself.
Oxford Cancer’s vision for fully leveraging this expertise is to provide support for these researchers, to combine their efforts and promote the analysis of carefully-selected patients with diverse immune-related diseases to yield the most information.
3. Inducing tumour-specific immunity and preventing escape
Oxford is home to numerous researchers with expertise in how the immune system detects and responds to infection and malignant transformation, as well as those with knowledge of how these processes are mitigated by factors in the tumour immune microenvironment.
Together, researchers are working to understand how cancer cells are able to evade the immune response, and develop new ways of both preventing and reversing it.
Oxford Cancer seeks to combine researcher efforts and promote the analysis of pre- and early stage cancers, with aim to ultimately develop a comprehensive model for the origins of tumour evasion.