BY JULIA EVANGELOU STRAIT

With the green light from the Food and Drug Administration (FDA), a new immunotherapy treatment is now available to treat certain adult patients with metastatic melanoma, an aggressive skin cancer that has spread to other parts of the body. Called tumor-infiltrating lymphocyte (TIL) therapy, this option is for people with metastatic melanoma that can’t be treated with surgery and that has continued to grow and spread despite already having been heavily treated with other approved strategies, including chemotherapy and immune checkpoint inhibitors.

The immunotherapy was approved under the FDA’s Accelerated Approval regulations, which allow for approval of drugs for serious illnesses or conditions that have an unmet medical need. For approval, such drugs are shown to have an effect that indicates a likely clinical benefit to patients—for example, improving how they feel or function, or extending survival. The Accelerated Approval pathway generally gives some people the opportunity to access a promising therapy while further trials are conducted to confirm the drug’s clinical benefits.

Siteman Cancer Center, based at Barnes-Jewish Hospital and Washington University School of Medicine, is one of the first centers nationwide to offer this new immunotherapy that targets melanoma. WashU Medicine physicians and researchers were involved in clinical trials that led to the FDA approval and continue to participate in ongoing clinical trials investigating TIL therapy for people with advanced lung and cervical cancers.

“These types of cell-based immunotherapies have been very impactful in blood cancers,” says George Ansstas, MD, WashU Medicine oncologist and leader of the solid tumor TIL program at Siteman. “More recently, in the solid tumor area, particularly melanoma, we have seen progress in developing effective cell-based immunotherapies, and this is the first to be FDA-approved. While metastatic melanoma treatment was revolutionized with immune checkpoint therapy—the first immunotherapy for cancer—and many of our patients do very well, at some point most patients have some kind of recurrence. Now, we have another option to offer.”

TIL therapy uses a patient’s own T cells that have already found and infiltrated the tumor in an attempt to kill the cancer. These natural cancer-killing immune cells can’t go it alone, though, because they are few in number and are quickly overwhelmed by the tumors. “This is truly personalized cancer therapy, because the T cells are taken from the individual patient’s tumor,” says Ryan Fields, MD, WashU Medicine surgical oncologist at Barnes-Jewish Hospital and co-leader of the Solid Tumor Therapeutics Program. “These T cells are already targeted in multiple ways to the specific cancer cells. And because the T cells belong to the patient, there is no risk of the immune cells attacking the patients’ healthy tissues—a dangerous condition called graft-versus-host disease—as can sometimes happen with stem cell transplantation for blood cancers.”

For the therapy, physicians take a sample of the tumor and send the tissue to a facility where tumor-infiltrating lymphocytes are isolated from the tumor and then expanded outside the body.

This TIL therapy cell product is then cryopreserved and shipped back to the patient. When returned to the patient’s body via intravenous infusion, the tumor-specific T cells—now numbering in the billions—are much more effective at killing tumor cells throughout the body. Patients receive a course of chemotherapy to prepare the body to receive the T cells. Patients also are treated with interleukin-2, which boosts T cell activity.

According to the results of a clinical trial reported in The Journal for ImmunoTherapy of Cancer, in about 30% of patients, the tumors shrank at least 30%. And about half of the patients whose tumors responded to the therapy experienced a remission of at least 12 months following a single TIL treatment.

Treatment includes chemotherapy to eliminate existing T cells and create space for the new T cells to take hold and trigger a heightened immune response. This can result in a range of side effects, including increased risk of infection, internal hemorrhage, heart arrhythmias, respiratory failure, kidney failure and allergic reactions. Many of the side effects can be managed well, but some are potentially severe and life-threatening. With that in mind, the first centers to administer TIL therapy are those with extensive expertise treating patients with cell-based immunotherapies, such as CAR-T cell therapy for blood cancers.

Originally published by Washington University School of Medicine.