Immune checkpoint blockade and head and neck cancer

Published on December 31, 2015   49 min

Other Talks in the Series: Immunotherapy of Cancer

0:00
My name is Jonathan Schoenfeld, I'm an Assistant Professor at Harvard Medical School and a Radiation Oncologist at the Dana Farber Cancer Institute with a clinical interest in immunotherapy and head and neck cancer. Today, I will be speaking about immune checkpoint blockade, and head and neck cancer.
0:18
Before I talk about tumor immunotherapy, I thought it would be useful to contrast the history of immunotherapy in a setting where we are all more familiar with its use, and that is in infectious disease. There was a great degree of skepticism when the first successful immunotherapy was developed in the 1800s in the form of a vaccination against small pox. As you can see in the cartoon on the left, there were significant public concerns that the material in the vaccination was derived from cowpox lesions. And indeed, no one volunteered to get vaccinated for over three months after this vaccination was first offered. Eventually, of course, small pox vaccination led to the near eradication of this disease. And just over a hundred years later, the practice of vaccination continued to revolutionize the field of medicine. As you can see in the figure on the right, there was no shortage of volunteers for the first successful polio vaccine in the 1950s. Indeed the lines for this vaccine stretched for blocks when it was first offered at the institutes for help in Washington, D.C. And this vaccination ultimately led to the near eradication of this disease. Obviously, the polio and smallpox vaccinations were just the beginning of the development of many other vaccines targeting other viruses. Currently, vaccination and immunotherapy remains of critical importance to public health worldwide in eradicating infectious disease.
1:48
Tumor immunotherapy has also taken a while to gain more broad acceptance in the medical community and among the public. The idea of using the body's immune system to combat cancer is not new, and dates back over 100 years to early experiments with infectious materials that I will discuss in the next slide. Unfortunately, for many decades, the role of the immune system in the development and treatment of cancer was relatively undefined. In 1909, the idea that the immune system might eliminate early cancers was initially proposed. In the 1950s there was evidence that at least some cancers resulted from viral infections, and could be transmitted in this manner. The first successful immunotherapy would also be related to infection. BCG, a material related to tuberculosis infection, which was found to cause local inflammation and inhibition of tumor growth in mice in the late 1950s, and would be subsequently approved for the treatment of localized bladder cancer in human patients in the 1970s. In the 1980s, interferon, a cytokine that stimulates the immune system, was developed as a treatment for melanoma. Unfortunately, although this treatment benefits a small group of patients, its toxicity limits its general use. But it was one of the first demonstrations that you could give a systemic agent to promote anti-tumor immunity and impact the outcome of cancer. More recently in 2010, the more modern age of immunotherapy received a huge boost with the FDA approval in the United States of two immunotherapy agents, including the first checkpoint inhibitor, ipilimumab for the treatment of metastatic melanoma. I'll speak quite a bit more about ipilimumab shortly. The other immunotherapy approved for treatment was sipuleucel-T for the treatment of metastatic prostate cancer. Development of immunotherapy has progressed rapidly in the last few years. In 2014, two additional checkpoint inhibitors, pembrolizumab and nivolumab, were approved for the treatment of melanoma in the United States. I'll also discuss the development of these agents in more detail. This year, 2015, has seen the further development of these agents in lung cancer, as well as in the first approval for combination therapy with ipilimumab and nivolumab in metastatic melanoma. The development of these agents continues very rapidly. According to a presentation at this year's 2015 American Society for Clinical Oncology Meeting, about one out of every 22 trials involving cancer patients currently ongoing in the United States and posted on a national database clinicaltrials.com, are related to the use of immunotherapy. Based on presented or published data, immunotherapy has now demonstrated efficacy across more than 12 tumor types.
4:43
Before we move on, given we'll be speaking about checkpoint blockade in head and neck cancer, I did want to point out that perhaps the first treatment with immune therapy for cancer anywhere, occurred in a patient with head and neck cancer. Dr. William Coley, shown on the left, was a surgeon practicing in New York, who noticed that some patients with severe infections could have regression of tumors, presumably because of the activation of the immune system. Because of this observation, he decided to inject advanced cancer patients with bacterial products, which came to be known as Coley toxins to see if he could recreate this phenomenon. He performed the first inoculation in 1891 on a patient called Zola, shown on the right. This patient had a tumor originating in the tonsil and interestingly, had a complete response following Coley's treatment and was able to live for an additional eight years after he was expected to die just weeks after he was first seen by Coley. Coley continued to try using infectious materials over the next several decades to treat advanced cancer patients. He had some successes, but the approach was toxic and unfortunately the majority of patients did not respond. The therapy never caught on more broadly with the medical community for a variety of reasons. One being the lack of a detailed understanding of how the immune system and the treatment was able to work in some patients.
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Immune checkpoint blockade and head and neck cancer

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