Interview with an Expert: Immunotherapy Update

About Our Expert: Elizabeth M. Jaffee, M.D., is an internationally recognized expert in pancreatic cancer and immunotherapy research. She is the Deputy Director at the Sidney Kimmel Cancer Center at Johns Hopkins and an Associate Director of the Bloomberg-Kimmel Institute for Immunotherapy. Dr. Jaffee serves as the Chief Medical Advisor for the Lustgarten Foundation as well.

Immunotherapy is touted as the pancreatic cancer treatment option of the future. It involves using a person’s own immune system to fight and destroy cancer cells and is considered by many leading researchers to represent a new and promising direction for cancer treatment. While immunotherapy has been successful in treating other diseases, only recently have we made breakthroughs in applying immunotherapy to pancreatic cancer treatment. Significant research involving immunotherapies is paving the way toward more promising pancreatic cancer treatment options for patients, although much more work needs to be done in this area.

How does cancer immunotherapy treatment options work?

Immunotherapy is a form of treatment in which we harness the immune system, which is meant to keep us healthy and fight infections and diseases. Cancer immunotherapy works similarly. The immune system is designed to recognize germs and viruses as invaders and get rid of these invaders so we remain healthy. Cancerous cells are invaders and can evade our immune system. Sometimes there are so many that the immune system becomes overwhelmed, and sometimes cancerous cells give off substances that stop the immune system from doing its job.

The goal of cancer immunotherapy is to help the immune system fight these cancerous cells. One way the immune system fights these cells is through the use of monoclonal antibodies, which are man-made antibodies or proteins that will target and destroy a specific part of a cancer cell. We can also use drugs like checkpoint inhibitors to give a boost to the immune system by “taking off the immune system brakes.” Once those brakes are off, the immune system can better recognize and then attack cancerous cells.

Another immunotherapy option involves the use of therapeutic vaccines, meaning they are designed to treat a disease, such as cancer, that’s already present. Doctors are also using patients’ own immune cells to treat their cancer, through a process called adoptive T-cell transfer. This approach has been tested in several clinical trials, resulting in significant responses for patients with advanced blood cancers. Trials are underway for solid tumors like pancreatic cancer.

How has our understanding of the immune system’s response to cancer changed?

There have been incredible strides made over the last 30 years in our understanding of cancer and the immune response. Today, through ongoing scientific research, we better understand the genetic drivers behind potentially life-threatening cancers. Technology has changed dramatically, especially molecular technology. We now have faster and less expensive genetic sequencing, and that means we can use treatments targeting the mutation that’s driving the cancer. We now know that pancreatic cancer has a minimal natural immune response.

However, I am confident that we will see progress in pancreatic cancer and other cancers that don’t naturally respond well to immunotherapy, and that’s due to a better understanding of the immune system. Mouse models are also helping to show inhibitory pathways within the pancreatic tumor microenvironment that prevent immunotherapy from working. We hope these models will provide valuable information that will lead to new immunotherapeutic opportunities.

Is immunotherapy treatment right for everyone?

We know that cancers with more mutations typically respond better to certain immunotherapy drugs. There have also been incredible stories of patients being cured of a particular cancer and stories of others who maybe only had a few months to live, gaining years through immunotherapy treatment. Despite these stories, immunotherapy only works for some patients, and researchers are trying to find out why. We know that immunotherapy is a powerful tool, but we still don’t fully understand it and we still can’t fully control it, so it is not right for everybody.

Patients who undergo immunotherapy treatment receive scans and other tests at intervals that are dependent upon the treatment protocol. More research is needed to determine how long a patient can stay on immunotherapy, and this research can vary, as every immunotherapy is different.

Are there any FDA-approved immunotherapy treatments available for pancreatic cancer patients?

The FDA approved pembrolizumab (Keytruda®) as the first immunotherapy treatment for advanced pancreatic cancer patients whose tumors have a unique genetic mutation called mismatch repair deficiency, which alters their capacity to repair DNA and is a factor in cancer development. Approximately 1-2% of pancreatic cancer patients have tumors with this mutation. To put that in perspective, an average cancer cell has approximately 70 mutations, while a mismatch repair deficient cell has about 1,700 mutations.

The Lustgarten Foundation supported this research on pembrolizumab, encouraged patients to get tested, and funded patients’ testing to determine if their tumors are mismatch repair deficient.

The Lustgarten Foundation envisions a world in which pancreatic cancer is curable and patients will be treated effectively through immunotherapy and other treatment options and enjoy a good quality of life. Find out more about our work as the world’s largest private funder of pancreatic cancer research.

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