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Next generation dreaming

As someone who has watched a close relative go through the experience of receiving chemotherapy, it is not something that I would ever wish upon any human being. The hypothesis for chemotherapy is simple. Cancer cells grow faster than normal somatic cells and thus if we inject poison into the body that damages cells, the cancer cells will die at an increased rate compared to ‘normal’ cells. While still currently the most effective way of treating cancer there are many, what I believe to be revolutionary, therapies that are being developed.

Immunotherapy makes use of the immune system to target cancer cells, however, the concept of ‘immune surveillance’ has been difficult to prove. It is defined as the immunological protection of the host against cancer development resulting from immune effector functions stimulated by immune recognition of either stress ligands or antigens expressed on transformed cells. There has been much debate over whether this concept actually exists, but a series of excellent experiments have concluded that it in fact probably does and that cancer immunosurveillance is part of a broader term ‘cancer immunoediting’. The term cancer immunoediting encompasses three main processes: immunosurveillance, editing and escape.

A variety of immunological therapies for the treatment of cancer have been explored in the clinic and which are showing success in patients. One that is highly relevant and related to the concept of cancer immunosurveillance is the use of checkpoint inhibitors. Three checkpoint inhibitors have been licenced so far: Ipilimumab (anti-CTLA-4), Pembrolizumab and Nivolumab, both of which are antibodies against PD-1. CTLA-4 and PD-1 both act as ‘immune checkpoints’ in the T-cell response to cancer. The purpose of these treatments are not to activate the immune system to target particular antigens on tumour cells, but to remove the inhibitory pathways that block effective anti-tumour responses.

Although these treatments have shown some success, they are only effective in a fraction of patients and resulting in efforts to obtain predictive biomarkers for which individuals might respond to treatment. PD-1 was investigated as a potential predictive biomarker, however, with the conclusion that it should not be used as a predictive biomarker for selection or exclusion of patients for anti-PD-1 therapy. A correlation of successful clinical responses and increased expression of neoantigens in the tumour environment with non-small cell lung cancer is perhaps something to investigate further.

Immunogenic tumours (i.e. tumours that can be recognised by the immune system) have the capacity to be successfully treated with checkpoint therapy, but in order to conclude that a tumour has an immunogenic environment, multiple components need to be evaluated. Combination therapies have the potential to create an immunogenic environment, through treatment with checkpoint therapy. As CTLA-4 and PD-1 have non-overlapping mechanisms of action, in 2015 Ipilimumab and Nivolumab were licenced for combination therapy in the treatment of advanced melanoma to try and increase the clinical benefit in response to the success of a phase III clinical trial showing that combination therapy was more effective than Nivolumab monotherapy.

In conclusion, there are many other exciting areas in the development of immunotherapy in addition to the ones that have not been discussed here, including the use of vaccines as a treatment for cancer with an example being the success of Phase II clinical trials for therapeutic vaccines against prostate cancer.

Olivia Bracken
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