With the announcement of our exciting new partnership with the British Society for Immunology, Dr Pippa Corrie, Consultant and Associate Lecturer in medical oncology in Cambridge and member of the NCRI Upper Gastrointestinal Group, talks about the breakthroughs in cancer treatment that have been achieved through immune-oncology, as well as the challenges that still lie ahead.
Immunotherapy as an anticancer treatment strategy has a history dating back over 100 years, but it has really only come of age in the last decade. In October 2018, Jim Allison and Tasuku Hojo were awarded the Nobel prize for medicine for their work in developing a revolutionary new class of immune checkpoint inhibitor antibodies, which has already radically changed standard of care for metastatic melanoma, non-small cell lung cancer and kidney cancer patients. In the last year, multiple new indications have received regulatory approval as clinical trials have repeatedly reported significant survival gains for a variety of different cancer types.
Checkpoint inhibitors block specific receptors on cytotoxic T cells to release the brakes on the immune system and stimulate tumour cell killing. The first therapeutic antibodies to enter the clinic have targeted CTLA-4 and PD-1 receptors. T cells are complex, possessing multiple receptors which interact with the microenvironment and many of these are now being explored for their therapeutic potential. Recently, trials of genetically engineered chimeric antigen receptors inserted into T cells (CAR-T cells) have reported stunning results in some patients. Multiple other therapeutic strategies are being proposed as more is known about both innate and adaptive immunity. Immunotherapy has captured the imagination of doctors and patients alike, raising the possibility that curing cancer might become a realistic prospect in the not too distant future.
Over 2,700 trials testing immunotherapy are currently listed on the clinicaltrials.gov website, the vast majority of which are either industry-sponsored or supported. All major pharmaceutical companies now own significant immunotherapy drug development pipelines, because immunotherapy is big business.
Big Pharma has the capability to move quickly to bring new agents to the clinic and this is clearly to the benefit of patients, as well as their share holders. Academia has worked in collaboration with industry, but the agenda of commercial and academic cancer research are not one and the same. There are so many key unanswered questions associated with immunotherapies already entering the clinic which are not the priority of Big Pharma which must now be addressed by academic teams across the world.
The clinical cancer research community is now entering a critical period when both the hype and hope that immunotherapy offers need to be critically appraised. Despite all the positive breakthroughs littering twitter, newspapers and medical journals, in 2019 it’s sobering to remember that most cancer patients treated with current immunotherapeutics will still die from their disease. Furthermore, a significant proportion of patients will experience life-threatening or life-changing toxicities due to their treatment – and fatalities do occur.
Can we predict up front who are the patients likely to respond – or not respond – to treatment, or who are at greater risk of life-threatening toxicities? How long does treatment need to be given for? If immune responsiveness is characterized by high tumour mutational burden and high T cell infiltrates, can we manipulate a cancer with low mutational burden and devoid of T cells and convert resistance to response?
In the UK, the NCRI Groups are grappling with many of these issues by developing clinical trials with translational elements, facilitating collection of critical patient samples – tumour, blood, stool – with linked response, survival and toxicity outcome data. Many cancer research institutes host immunologists as laboratory group leaders, studying complex relationships between tumour, host and microenvironment and oncologists now need their help if we are to advance cancer immunotherapy beyond the current state of play.
The NCRI has just agreed a new partnership with the British Society for Immunology (BSI) aimed at building closer relationships and interactions between our two communities. This exciting new initiative will encourage cross-talk, data sharing, access to and analysis of patient samples, providing opportunity for new research to flourish and the full potential of immunotherapy be achieved.