The Cinderella of cancer treatment strategies: Immunotherapy finally comes of age
by Dr Lee Machado, Senior Lecturer in Biochemistry
Recent reports in the news this week have discussed the revolutionary use of a cancer combination treatment that provides a one-two punch to cancer cells. The National Institute of Clinical Excellence (NICE) has rapidly approved the combination of two drugs called Nivolumab and Ipilumimab for the treatment of cancer. These drugs work by removing the breaks on the immune system, by blocking molecules that act as a stop-signal for the immune system to act (so-called checkpoint blockade inhibitors).
Standard treatment for cancer involves surgery, radiotherapy or chemotherapy, and the specific regimen and combination of treatment will depend on the particular cancer a patient has, as well as other factors like the stage and grade of the tumour. However, some cancers respond very poorly to conventional treatment and malignant melanoma (a form of skin cancer) is one such example where patients with advanced stage disease typically have tumours that are highly aggressive and rapidly spread to other distant sites in the body.
For many years we have known that when you look at a tumour like melanoma, in addition to the tumour cells, there are also white blood cells of the immune system (called lymphocytes) that have migrated into the tumour, and appear to be interacting within that microenvironment. It has remained a mystery as to why these immune cells have not been able to eradicate the tumour cells given their close proximity and interaction with them. Several decades of research to answer this question appear to provide a number of answers. For example, immune cells at tumour sites are often inhibited in their ability to recognise and destroy the cancer cells; Suppressive cells might be present in the tumour and can prevent the lymphocytes from functioning. Alternatively, the tumour cells may be producing factors that allow it to directly evade detection by the immune response.
In developing immunotherapy in the laboratory over a number of projects, we have explored different immunotherapy strategies to target cancer. For example, in work with investigators at Birmingham we have used gene modified lymphocytes to show proof-of principal for more effective targeting of viral cancers (including those of the nasopharynx and certain lymphomas). More recently, with the biotech company Scancell we have evaluated a DNA vaccine in a phase I/II trial that induces the immune system to respond more effectively in melanoma patients. Closer to home in Northampton, PhD student Nina Albalbeisi is exploring the possibility that an enzyme, if expressed strongly in ovarian tumours, may act to flag the cancer cells for destruction by the immune system.
There are still many challenges ahead in the development of these novel immunotherapies. Both Nivolumab and particularly Ipilumimab can have potent side effects for cancer patients but the exciting prospect is to combine these checkpoint blockade drugs with complementary approaches like cancer vaccination to improve outcomes for cancer patients. If this goal can be achieved, then the future of cancer immunotherapy and that of cancer patients may be a brighter one.
