Cancer Immunotherapy

24/03/2016 09:42 GMT | Updated 23/03/2017 09:12 GMT

The relationship between a patient's cancer and their immune system is a complex tug-of-war. This begins with recognition and efficient rejection of developing cancers by the immune system in a similar way it treats infecting microorganisms, but may potentially end through several stages where a cancer establishes, a tumour forms, and this cannot be contained. Understanding the mechanisms underlying these stages is finally bearing fruit with astonishing advances in immune-based treatment for cancer patients over the last 5 years. Prior to this we have accumulated compelling evidence of immune activation leading to cancer regression and sometime cure in a small number of patients with specific cancers (e.g. patients with kidney and skin cancers treated with a substance made by activated immune cells (T cells) called interleukin-2 (or IL-2)) or the broader application of immunotherapy with antibody therapy (drug like Herceptin and Rituximab) for common cancers in combination with traditional cancer therapies.

The focus of many research groups has centred around trying to re-awaken the patient's immune system which has become 'tolerant' to the presence of cancer. Curiously, this is highly effective if a patient's own cancer is removed, its growth nullified in the laboratory and then re-injected into the same patient. Where this is not possible (i.e. no tumour tissue is accessible for removal), cancer cells from a similar patient cancer or proteins/peptides stripped out of cancer cells may be almost as effective. With repeated injections of this material, which the body perceives as new cancers, are augmented by an immune booster (called an adjuvant). These immunisations into the skin are repeated over many months. In almost every trial, evidence of immune activation is demonstrated in blood tests, but these 'vaccines' have, to date, had little impact on tumour shrinkage or increasing patient longevity.

So what is the excitement about? This centres around the realisation that as well as common abundant cancer-related proteins on the cancer cell being recognised, new proteins as a result of genetic mutations in the cancer cells being generated. Normally the immune system would register these and subdue any response. However, the a new generation of agents are able to work directly at this mechanism, take the brake off the process of suppression and allow the body immune T cells to become highly activated, proliferate and spread around to destroy cancer deposits at many sites. The agents are antibodies called 'checkpoint inhibitors', given as 3 weekly infusions which allow the patient's immune system to 'raise its game' and specifically amplify the immune response against the cancer-associated genetic mutations. As a result, we are improving survival of patients massively from several months to several years with huge impacts of quality of life and symptom control. Cancers with high numbers of mutations ( bladder cancer, lung cancer) originally thought resistant to immunotherapy have provided among the most striking clinical data. Combined with other compelling approaches such as the use of T cells specially engineered in the laboratory to treat certain leukaemias (CAR T cells) and the recent approval by the FDA of a cancer-killing (oncolytic) virus which generates a vaccine effect (T VEC), immunotherapy has finally come of age and will be considered routinely in the overall treatment plan for many patients soon.