Patients with pancreatic cancer often ask Dana-Farber’s Brian Wolpin, MD, MPH, about immunotherapy, the rising star of cancer treatment that’s making impressive gains against many types of malignancies.
Immunotherapy drugs, which mobilize the patient’s immune defenses to recognize and attack tumor cells, have worked against lethal cancers such as melanoma and some lung cancers – sometimes with dramatic success – and are being tested in dozens of other cancer types. Some of the newest such drugs, called checkpoint inhibitors, work by freeing the immune system to respond against the cancer.
But pancreatic cancer has proven difficult to treat with conventional drugs, and it has proven resistant to initial immunotherapy approaches. Wolpin and other scientists are now testing immunotherapy combinations and devising innovative strategies they hope will bring greater success.
Pancreatic tumors develop deep within the body and surround themselves with a tough, fibrous capsule that’s difficult for drugs to pierce. This also wards off the immune system’s T cells, which attack foreign invaders and cancer cells within the body. With pancreatic tumors, T cells are “trapped outside the tumor and unable to penetrate it,” explains Wolpin, of Dana-Farber’s Gastrointestinal Cancer Treatment Center. “There are also other cells that suppress T cell entry into the tumor.”
Nevertheless, scientists are exploring an array of strategies aimed at smuggling T cells and other immune weapons into pancreatic tumors. Stephanie Dougan, PhD, of Dana-Farber’s Department of Cancer Immunology and Virology, is studying the barriers to T cell entry, and the use of antibody fragments to deliver immune-stimulating proteins called cytokines to pancreatic tumors in animal models.
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Wolpin is leading a clinical trial in which patients receive a standard chemotherapy drug along with an experimental compound designed to block suppressor cells called macrophages that help defend pancreatic tumors from immune attack.
He is also leading participation by the Dana-Farber/Harvard Cancer Center (DF/HCC) in a new, large-scale precision medicine pancreatic cancer trial that includes immunotherapy agents. DF/HCC is one of the 12 initial clinical trial consortium sites for the Precision Promise Initiative, launched in October by the Pancreatic Cancer Action Network. Dougan, who won a Pathway to Leadership award from that organization, serves on the Precision Promise Immunotherapy working group.
Wolpin says the Precision Promise trial has a unique design that enables patients to receive multiple experimental treatments during the course of their disease.
“It will allow patients to get a first line of therapy, and then, if their tumor becomes resistant to the therapy, proceed to a second, and then to a third therapy, all under the same framework. Other trials usually offer only one experimental drug in a single setting.”
Learn more about symptoms, risk factors, and treatments at the Pancreas and Biliary Tumor Center at Dana-Farber/Brigham and Women’s Cancer Center.