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In 2012, there were an estimated 14.1 million new cases of cancer and 8.2 million cancer deaths. By 2030, these numbers are expected to increase to 21.7 million and 13 million, respectively, mostly as a result of growing and rapidly ageing populations, but also due to the increasing prevalence of western lifestyles such as smoking, physical inactivity and poor diet, in the developing world. In recent years, our increasing knowledge of the causes of cancer and intense research and development has led to the introduction of innovative and effective cancer screening methods and treatments, so the word “cancer” should not automatically strike terror in us.
Over the last 20 years, the age of standardized cancer mortality rate has decreased by ~1% per year in the United States, Europe and other high income areas. For example, the introduction of cervical screening programs and routine human papilloma virus vaccination in 71 countries has reduced the number of new cervical cancer cases by 50%. The introduction of cisplatin has been instrumental in reducing testicular cancer mortality by two-thirds in the United States since 1975. However, there is still an urgent need for more effective treatments for cancers that are difficult treat such as pancreatic cancer, and also for ‘’kinder’’ treatments.
Cancer immunotherapy is an exciting, relatively new therapy that treats cancer by unleashing the power of the immune system; in contrast to the conventional therapies of radiation therapy and surgery, which disrupt it and can cause debilitating side effects, including nausea, fatigue, hair loss and myelosuppression. In fact, the American Society of Clinical Oncology designated cancer immunotherapy as the 2016 Advance of the Year.
The immune system has unique properties, including its memory capacity, specificity and its role in human biology, so immunotherapy has the potential to cure a wide range of cancers and give long-lasting remissions with reduced side effects. It’s the most promising new cancer treatment approach since the advent of chemotherapy in the 1940s and is an ever growing area of clinical research.
The main types of cancer immunotherapy are:
- Monoclonal antibodies (mAbs) designed to target antigens or markers on the surface of cancer cells, so that they are marked for destruction by immune cells.
- Immune checkpoint inhibitors that block the ability of cancer cells to use checkpoint molecules to escape from the immune system and reactivate T cells, B cells and other cells to destroy cancer cells.
- Cancer vaccines that initiate an immune response against cancer cells without affecting healthy cells.
- Oncolytic virus immunotherapy using genetically modified viruses to kill cancer cells.
- T-cell therapy that involves modifying T-cells removed from a patient’s blood so that they include receptors allowing recognition of cancer cells and then re-administering the cells.
Rituximab is a chimeric monoclonal antibody against the CD20 antigen on the surface of B cells and was the first antibody treatment for cancer approved by the US Food and Drug Administration (FDA) in 1997. Rituximab is sold by Roche as Rituxan® and is used for treating non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). It is the best-selling anticancer drug, generating $7.10 billion in global sales in 2015 and it is still expected to generate $5 billion in annual sales in 2020, despite losing US patent protection in 2015. Rituxan® has a 5 year relative survival rate of 70% and a 10 year relative survival rate of 60%. Roche is hoping that another anti-CD20 monoclonal antibody called Gazvya® (obinutuzumab) that was approved by the FDA in 2013 and is used for treating CLL, will be equally lucrative.
In March 2011, the FDA approved Yervoy ® (ipilimumab) from Bristol-Myers Squibb as the first immune checkpoint inhibitor for treating advanced melanoma. It is a monoclonal antibody that inhibits cytotoxic T-lymphocyte-associated protein 4 (CTLA-4).
Keytruda® (pembrolizumab) from Merck was approved in September 2014 and is used for treating metastatic melanoma, non-small cell lung cancer (NSCLC), Hodgkin’s lymphoma and head and neck cancer. It is best known for successfully treating brain cancer due to metastatic melanoma in former President Jimmy Carter. Opdivo® (nivolumab) from Bristol-Myers Squibb and Ono Pharmaceuticals was approved in December 2014 and is used for treating advanced melanoma, advanced lung cancer, advanced kidney cancer, bladder cancer, Hodgkin’s Lymphoma and squamous cell carcinoma of the head and neck. Keytruda® and Opdivo® are both programmed death receptor-1 (PD-1) inhibitors.
Genentech has developed Tecentriq® (atezolizumab) as the first PD-1/PD-L1 inhibitor and in May 2016, it was approved for treating urothelial carcinoma and advanced NSCLC. In March 2017, Bavencio® (avelumab), a PD-L1 blocking antibody, received accelerated FDA approval for treating metastatic Merkel cell carcinoma in patients at least 12 years of age.
Several antibody-drug conjugates have been approved by the FDA, including Adcetris® (brentuximab vedotin) for treating Hodgkin and anaplastic large cell lymphoma. The antibody allows binding to a target molecule on the surface of cancer cells. Researchers are combining parts of two antibodies to form a bispecific antibody, where one part attaches to a cancer cell and the other attaches to an immune cell. This may produce a more effective immune response and prevent the immune system reacting against itself to produce side effects and destroying the mAbs. Researchers are also combining drugs that have different targets. Nivolumab, which targets PD-1, and ipilimumab, which targets CTLA-4 have been shown to be more effective in treating melanoma than using either treatment alone.
Cancer immunotherapy has captivated the imagination of the general public and researchers, but does the reality match the hype? Results can be extraordinary, but some studies suggest that only a small number of cancer patients benefit from immunotherapy. A study carried out by Prof. Vinay Prasad and Dr. Nathan Gay from the Oregon Health and Science University, using US national cancer statistics and FDA approvals up to February 2017, determined that no FDA approved immunotherapies are available for 68.8 percent of Americans predicted to die of cancer and only 26 percent of patients could expect their tumors to shrink as a result of immunotherapy. Combining the calculations showed that only 8 percent of Americans dying from cancer in 2017 might benefit from administration of an immune checkpoint inhibitor.
Typically, the side effects of immunotherapy are uncommon and mild, but they can be life threatening. There is some evidence to suggest that immunotherapy may increase the growth of tumors in some patients. In a study at the Gustave Roussy Institute in France, of 131 patients, 12 patients exhibited hyperprogressive growth after taking anti-PD-1 or anti-PD-L1 immunotherapies. It may be possible to identify these “at risk” patients by genetically testing tumors.
Maybe our initial excitement and enthusiasm for immunotherapy should be tempered by the limited number of approved therapies and the potential side effects. However, as researchers learn more about the interactions between our immune system and cancer and carry out more clinical trials, we can look forward to the development of more effective immunotherapies in the future.
“This is clearly a major advance for cancer. This is a great example of how scientific knowledge has been converted into a new preventive or treatment strategy that has had a profound impact on a number of different cancers. If we can activate the immune system, the immune system is then very well designed to recognize the cancer as foreign and attack it.”
– Dr. Ron DePinho president, University of Texas MD Anderson Cancer Center
To learn more, read the State of Innovation report on the Biotechnology industry, or download the full 2017 report here, which showcases latest inventions from around the world and focuses on trends in the top 12 industries.