The 2018 Nobel Prize in Medicine was announced on 1 October and was awarded to two scientists – Dr. James P. Allison of the United States and Dr. Tasuku Honjo of Japan “for their discovery of cancer therapy by inhibition of negative immune regulation” – a discovery that has wide reaching implications in the field of oncology.
For decades, the mainstay of cancer treatment continued to be chemotherapy, radiotherapy and surgery. However, while most of the attention was focused on the disease and the factors that lead to its progression in the human body, Allison and Honjo focused on the immune response to it – more precisely, on how the immune response was affected by cancer. Indeed, this year's Nobel is the first time that the development of a new cancer therapy has been rewarded by the committee.[pullquote]Former US President Jimmy Carter was one of the recipients of Keytruda for melanoma that had spread to the brain and liver. His last scan in June 2018 showed no signs of cancer, his aide said.[/pullquote]
Allison and Honjo, independently of each other, worked on two different proteins (CTLA-4 and PD-1 respectively) found to be “brakes” that under normal circumstances, would act as mechanisms of control – preventing the body’s immune cells from attacking normal human tissue. While enhancing the function of these proteins was a key aspect of research which tried to combat autoimmune diseases (conditions where the body’s immune system perceives normal human tissue as foreign and attacks it resulting in an abnormal immune response), Allison went the other way and removed the brakes – thus unleashing an overactive immune system against a disease whose hallmark is uncontrolled proliferation. Honjo discovered another protein also functioning as a brake – albeit with a different mechanism of action - and further work from the man who is a professor now at Kyoto University, led to what is now a mainstay in clinical treatment for various types of cancer including lung cancer, melanoma and renal cancer among others.
The drugs that have come out over the years as a result of this pioneering work are part of a group called the checkpoint inhibitors, including ipilimumab (brand name Yervoy), nivolumab (Opdivo) and pembrolizumab (Keytruda). Former US President Jimmy Carter was one of the recipients of Keytruda for melanoma that had spread to the brain and liver. His last scan in June 2018 showed no signs of cancer, his aide said.
While the advances are remarkable to read about and have changed the lives of millions, challenges do exist – as they inevitably do when it comes to science. Immunotherapy, as this treatment is called relies on a hyperactive immune system to counteract an uncontrolled disease. However, this can result in inflammation of various organs unconnected to the disease itself because the T-cells (one of the components of the immune system) attack normal tissue. The lungs, pancreas, heart, intestines and the thyroid have all been affected by this.
Doctors in the clinic, however, are adapting and are able to manage the side-effects better than before. The future of this field lies in trying to identify more such proteins that act as checkpoints in the immune system – something that could allow for alternative options of treatment and help a wider cohort of patients – while trying to minimise the side-effects of the drugs that are produced as a result of the work done on these proteins. There are multiple clinical trials being run across the world to this end and hopefully, someday, they can result in a massive difference to the millions across the world affected by the disease.