Throughout human history, from ancient Egyptians who blamed cancers on the gods, to Hippocrates who believed that cancer was caused as a result of an excess of black bile in the body, physicians have tried to understand and treat the disease. In ancient Rome surgery was the only real option and this became the status quo for physicians for the best part of two millennia. With the development of anesthesia in the 19th century surgery became more advanced; however it still had severe limitations, particularly for people in the metastatic stage, where cancer has spread.1
During the same period the idea of immunotherapy first began when a New York based surgeon, William Coley, started treating cancer patients with different types of bacteria as a means of stimulating the immune system to fight the disease. While this approach yielded limited success, it was because of Coley’s work that the concept of immunotherapy became indelibly forged into the thoughts of generations of oncology scientists.
In 1903, five years after Marie Curie’s discovery of radium, the first patients were successfully treated with radiotherapy. This type of treatment uses high-energy rays to destroy cancer cells. At the time it was a huge step forward and it is still used today. It has, however, its limitations, damaging normal cells in the process, which may cause side effects.2
The next notable treatment development was the advent of chemotherapy which was first discovered during the Second World War, with the first cure of metastatic cancer coming in 1956.3 At the time this represented a major breakthrough and provided real hope to patients. Chemotherapy has evolved over the intervening 70+ years and is far more sophisticated than it once was, but it still works by fundamentally destroying cancer cells, in particular by targeting rapidly dividing cells. Whilst cancer is destroyed, so are other normal cells, including cells in the blood and bone marrow. As a consequence, an unwanted by-product of chemotherapy is the destruction of healthy cells, such as white blood cells, which can make people more vulnerable to infection.
A major step forward in cancer treatment came with the development of targeted cancer therapies – a type of treatment that blocks the growth of cancer by interfering with specific molecules. Whereas most standard chemotherapies act on all rapidly dividing cells, both normal and cancerous, targeted treatment acts on specific targets that are associated with cancer.4
The latest area of innovation is in cancer immunotherapy which works specifically in the immune system. We tend to think of the immune system as the body’s defence force against invaders – the viruses and bacteria that make us sick. This is the reason why it has evolved over time to protect us.
The immune system detects and destroys anything that shouldn’t be in our bodies – including normal cells that have become cancerous – by recognising the often subtle changes that can make a normal cell ‘foreign’. Normally, the immune system works to eliminate these foreign or abnormal cells by using T cells to seek out and kill potential threats. In some cases these mutated cells can evade the immune response, allowing them to develop into potentially harmful tumours.
By understanding the biology of cancer and understanding how the immune system works cancer immunotherapies have been developed. The goal for these types of drugs is to help the immune system recognise and attack cancer cells. Immunotherapies do this in different ways, some seek out and override the mechanisms that are preventing T cells from mounting an immune response and others seek to stimulate an immune response.
Immune biology and cancer is a very complex science, but by knowing which aspect of the biology to target, scientists can tailor the use of cancer immunotherapy treatments to a person's specific type of tumour.
Robin Taylor, Vice President, Cancer Immunotherapy at Roche, explains where we have come from and where the science is leading us:
Cancer immunotherapy represents an exciting and ever-expanding area of research, which may change how we think about and treat cancer in the future. This expanding knowledge of the immune biology, and how we can enhance and aid the body’s own immune system to fight cancer, provides a reason for optimism now and in the near-term future.
As our understanding of the immune system and tumour biology expands, so does our hope for developing treatments that may change people’s lives. In recent years progress has been made in developing cancer immunotherapies that target specific aspects of an individual’s tumour. In the future, and even in some cases today, combinations of different treatments will hopefully advance this even further. This is an extremely complex area of research but is one that is being investigated now, with progress being made. The future of cancer immunotherapy is an exciting one.
Dr. Daniel Chen explains how immunotherapy may affect the PD-L1/PD-1 pathway, enabling the body to better detect and fight cancer.