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School of Medicine
Dome - Putting the Fight Back in Immune Cells
Dome May 2014
Putting the Fight Back in Immune Cells
Date: May 1, 2014
Melanoma Program director Suzanne Topalian, center, with lab members, from left, January Salas, Tracee McMiller and Shuming Chen, work on a therapy to help the immune system attack cancer.
Restoring the immune system’s ability to spot and attack cancer is not an easy task. Some therapies, like cancer vaccines, attempt to coax immune cells in patients’ bodies to attack cancer. Others use antibodies, which are proteins that target and bind to certain molecules on the surface of tumors or tumor-promoting cells.
Another promising experimental therapy is the focus of laboratory studies and clinical trials led by Johns Hopkins Sidney Kimmel Comprehensive Cancer Center investigators Suzanne Topalian, a professor of surgery and oncology, and Julie Brahmer, an associate professor of oncology.
This new type of immune-based therapy aims not to kill cancer cells directly, but to block a pathway that shields tumor cells from the immune system components that are potentially able to fight them. The pathway includes two proteins called programmed death-1 (PD-1), expressed on the surface of cancer-fighting immune cells, and programmed death ligand-1 (PD-L1), expressed on cancer cells.
When PD-1 and PD-L1 join together, they form a biochemical shield that protects tumor cells from being destroyed by the immune system. The new approach is designed to weaken the shield by blocking the pairing of PD-1 and PD-L1.
“We think immunotherapies like the ones we are studying may help lift the veil on cancer cells within the body so that immune cells can find and destroy them,” says Brahmer, principal investigator on clinical trials involving this approach at the Kimmel Cancer Center.
Results of a clinical trial testing the therapy, published online in March 2014 in the Journal of Clinical Oncology, showed encouraging results in patients with melanoma—the deadliest form of skin cancer. Patients who responded to a PD-1-blocking drug called nivolumab survived for an average 16.8 months following initiation of treatment, and some are still in remission for more than three years. Overall, 62 percent of the patients were alive one year after starting this treatment, and 43 percent were alive two years later. The drug is now being tested in melanoma patients in larger, phase III trials that will compare the new therapy with standard therapies currently in use, says Topalian, who directs the Kimmel Cancer Center’s Melanoma Program.
Johns Hopkins cancer researchers also describe broad success using the same approach for kidney and lung cancers, and some favorable responses to the therapy have been reported in stomach, ovarian, breast, head and neck, and bladder cancers.
To decipher precisely how the PD-1-blocking therapy works, Topalian and colleagues have gone back to the laboratory. By studying immune cells and tumor biopsies from patients who received nivolumab, they have found that the drug can remain latched onto immune cells for up to three months, indicating the potential for long-lasting antitumor activity.
Ongoing cancer immunology studies by Johns Hopkins researchers Drew Pardoll, Charles Drake and Janis Taube are expected to further unveil the cellular mechanisms by which PD-1 blocking compounds and other similar drugs work.
“Ultimately, we envision boosting the effectiveness of the therapy by combining it with anticancer vaccines and other anticancer drugs,” says Pardoll.