Welcome to Partners in Pancreatic Cancer. I am Dr. Ramesh Ramanathan. I am the Co-Chair for the Pancreatic Cancer Disease Group at the Mayo Clinic Cancer Center based in Phoenix, Arizona. I am frequently asked, “Will immunotherapy have a future role in advanced pancreatic cancer?” I think the answer is yes. I am optimistic about it, despite the recent negative studies with a number of single-agent checkpoint inhibitors and vaccines. I think there will be major advances soon. For example, we actually have one immunotherapy drug for pancreatic cancer, which is pembrolizumab, which is approved for MSI high tumors including pancreatic cancer. In pancreatic cancer, MSI high tumor is uncommon, probably in the 1% to 2% range, but that is still a treatment option for pancreatic cancer. There are a number of barriers in development of immunotherapy agents for pancreatic cancer. This includes the dense stroma and the immunosuppressive environment which prevents T-cells and agents from entering the tumor cells. A lot of work has been going on to try to develop new agents and I think most importantly, is the development of new mouse models. The mouse models that we have now which I use for cytotoxic chemotherapy are not suitable for immuno-oncology development and new mouse models with immunocompetent mice are being developed. I think the future is in combination therapy of immunotherapy drugs with the vaccines or even chemotherapy. We have seen some chemotherapy drugs, immunostimulants, especially given in different schedules or low doses. There is also a lot of work in combining the checkpoint inhibitors and CTLA-4 inhibitors with co-stimulatory molecules such as dendritic cells.
A number of strategies are being looked at with the immuno-oncology agents. We have seen that pancreatic cancer has a low mutational load in comparison with other tumor types, which have high mutational loads, such as melanoma and lung cancer where we have seen single-agent checkpoint inhibitors being active. Scientists and clinical investigators are working on combining a number of new agents such as CD40 IDO inhibitors in combination with the checkpoint inhibitors that are in clinical practice, such as nivolumab and pembrolizumab. I think the future certainly looks promising, but we have a lot of work to do and this includes proper use of mouse models and appropriate clinical trials in selected patients. Thank you for viewing this activity.