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Cell Therapy is Now on The Table for Metastatic Melanoma

Targeted Cell Therapy - Treatments that Use Drugs Designed to Target Anomalous Cells without Affecting Healthy Cells
Article Summary
  • The first cell immunotherapy for a solid tumor was recently approved by the Food and Drug Administration for metastatic melanoma patients.
  • The therapy, known as tumor-infiltrating lymphocyte therapy or TIL, will soon be available to patients at Sylvester.
  • Sylvester will be launching a clinical trial testing modifications to improve TIL responses even further.

There’s good news for patients with advanced melanoma.

The first cellular therapy for metastatic melanoma was recently approved by the FDA. This is the first cellular therapy approved for any solid tumor and is meant to treat advanced cases of the skin cancer where previous treatments have failed.

The therapy, known as tumor-infiltrating lymphocyte therapy (TIL), uses a patient’s own immune cells to battle their cancer and will soon be available to patients at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine.

Florida has the second-highest total number of new melanoma cases per year in the U.S. Sylvester will be the only center in South Florida to offer the newly approved therapy.

Researchers at Sylvester will also soon be part of another clinical trial led by the TIL manufacturer, Iovance Biotherapeutics, to test certain modifications of the immune cells, with the aim of improving their efficacy even further.

Testing Tumor-infiltrating Lymphocyte Therapy

Trials testing the newly approved TIL therapy, lifileucel, showed a response rate of 32% among 153 participants. The therapy is approved for patients whose melanoma has advanced despite treatment with other forms of immunotherapy, namely checkpoint inhibitors and targeted therapy, which is used for melanomas that carry a common mutation in the BRAF gene.

Targeted Cell Therapy - Treatments that Use Drugs Designed to Target Anomalous Cells without Affecting Healthy Cells
Dr. Jose Lutzky says cell therapy is a major advance for patients with advanced melanoma.

“Cell therapy has now become a viable option for patients with advanced melanoma,” said Jose Lutzky, M.D., a skin cancer physician and director of cutaneous oncology at Sylvester. “The trial results represent a major advancement for our patients.”

In the clinical trial that led to lifileucel’s approval, more than half the patients whose cancer responded to the therapy had maintained that positive response more than three years later.

Harnessing a Patient’s Own Immune Response

TIL therapy has been studied in the lab and in clinical trials for decades. The approval of lifileucel in February is the first FDA approval for any TIL treatment.

Tumor-infiltrating lymphocytes are naturally occurring immune cells that make their way inside tumors to try to fight them. They’re made up of a mix of different kinds of white blood cells, T cells and B cells. To boost their natural cancer-killing abilities, the method involves surgically removing a patient’s tumor, isolating the lymphocytes inside that tumor and growing them to large quantities in a special manufacturing facility before reinfusing them back to the patient.

Unlike other forms of cell therapy, such as CAR-T or T-CR cell therapy, the lymphocytes aren’t genetically engineered to recognize cancer. They are already specifically tuned to that patient’s tumors. The method also involves treatments after infusion to activate and stimulate the lymphocytes in the patient’s body.

The surgery, high doses of chemotherapy needed before infusion and the subsequent treatments can be hard on patients, Dr. Lutzky said. Those with heart conditions or other health problems may not be able to tolerate the treatment.

“These are not easy treatments, but many patients do have great responses,” Dr. Lutzky said.

Tweaking TILs

Dr. Lutzky hopes to open enrollment for Sylvester’s participation in the phase 2 Iovance trial soon and enroll around 10 or more patients in the next year. This clinical trial will enroll patients with advanced melanoma whose previous treatments have failed.

The trial will test a variation of TIL therapy in which the immune cells are genetically engineered in the lab to remove a gene called PD-1. The PD-1 protein acts as a natural block on immune cell activity. Cancer cells often hijack this process to switch off the body’s immune cells.

Removing PD-1 from the lymphocytes may enhance their cancer-killing ability in the body, Dr. Lutzky said. Laboratory studies and an earlier stage clinical trial of these modified cells showed that they are just as active as the non-engineered lymphocytes.

A Journey to Better Treatments

Before he joined Sylvester, Dr. Lutzky participated in clinical trials that led to FDA approval of another immunotherapy for metastatic melanoma, a checkpoint inhibitor called ipilimumab. Before the advent of immunotherapies, physicians were limited in options they could offer patients with advanced melanoma, he said.

Melanoma is very responsive to the immune system. Some immunotherapies work better in this cancer than in other cancer types. Melanoma was also the first cancer for which checkpoint inhibitors were approved.

But as researchers have learned about immunotherapy principles in these more responsive tumors, they’ve been able to extend those findings to other kinds of cancer as well.

“Melanoma was the first tumor where checkpoint inhibitors were found to be effective, and established what we now call the fourth pillar of cancer treatment, adding immunotherapy to surgery, chemotherapy and radiation,” Dr. Lutzky said. “It’s been a really amazing journey that’s happened in melanoma.”

Tags: Dr. Jose Lutzky, immunotherapy, melanoma, Sylvester Comprehensive Cancer Center