Abstract

Beyond Checkpoint Inhibitors, New Opportunities In Immuno-Oncology

Stuart Farrow, Director of Biology, Cancer Research Technology

The recent remarkable progress in cancer immunotherapy has emphasised the critical importance of understanding the full spectrum of tumour- immune system interactions and how they might be modulated for clinical benefit. Although the concept of using the immune system to target cancer has been recognised for many years, until recently despite intensive research, efforts to realise this have been largely discouraging. One of the major challenges has been the concept of immune tolerance, and recent success with novel therapeutic approaches that break immune tolerance in the tumour has fuelled significant new enthusiasm for cancer immunotherapy. Current breakthroughs have focussed on T-cell- tumour interactions, exemplified by antibodies targeting the T-cell proteins CTLA-4 and PD-1. However it is already clear that the known repertoire of additional “checkpoint” receptors expressed on T-cells may represent additional therapeutic targets to modulate immune tolerance. Looking further into the future, it is exciting to recognise that these direct T-cell tumour interactions are only one aspect of the full tumour immune cycle, and that other well characterised areas of immunology such as immune cell trafficking and antigen presentation now represent new areas for therapeutic discovery in oncology. Furthermore it is also clear that the fields of viral and infectious disease immunology will almost certainly be sources of new therapeutic approaches for cancer, and that consequently an overarching understanding of how to modulate immune tolerance will have enormous implications for clinical benefit across many important human diseases.