Cellular Therapy May Be Viable Option for Advanced Melanoma Patients
In the past decade we have seen an emergence of immunotherapies to treat cancer, especially melanoma. These therapies utilize the patient’s own immune system to fight their disease. Some of the earliest types of immunotherapies approved for melanoma include immune checkpoint inhibitors. These drugs target a specific protein, such as PD-1 or CTLA-4, that is stopping the immune system from recognizing and attacking cancer cells. This therapy, whether given alone or as a combination treatment, can lead to durable responses for nearly half of melanoma patients with advanced disease. But what about the other half of patients whose melanoma progresses despite this kind of immunotherapy?
Moffitt Cancer Center has been at the forefront of a new type of immunotherapy called cellular immunotherapy. This therapy involves using immune cells instead of drug compounds or molecules to fight cancer. One type in particular, tumor infiltrating lymphocyte therapy or TIL, has shown promise in melanoma and other solid tumor cancers. For TIL, surgeons remove a patient’s tumor and send it to a lab. The tumor is then minced to allow recovery of the tumor infiltrating lymphocytes – T cells that have been able to penetrate the tumor. These cells, which can detect and invade the tumor, are then multiplied by the billions in a process that takes about three to four weeks. Once infused back into the patient, the army of T cells can seek and kill the cancer cells.
Dr. Amod Sarnaik, medical oncologist
“TIL therapy has been used in an investigational setting for more than three decades, mostly for melanoma patients who have not received prior immunotherapies,” said Dr. Amod Sarnaik, a physician scientist in Moffitt’s Department of Cutaneous Oncology. “However, we know the potential of this therapy, which is why we are evaluating TIL as an option for melanoma patients with advanced disease who may have seen initial responses to immunotherapies, such as immune checkpoint inhibitor therapy, but relapsed or had disease progression.”
Sarnaik is principal investigator of the phase 2 multi-center trial, in collaboration with Iovance Biotherapeutics. It is considered the largest cell therapy study in advanced melanoma patients who have received previous immune checkpoint inhibitor therapy. Results from study cohorts 2 and 4 are being presented at the 2022 Society for Immunotherapy of Cancer Annual Meeting.
Cohorts 2 and 4 included 153 melanoma patients who, on average, had three or more prior therapies. Each underwent surgery to remove their tumors, which were shipped for centralized TIL manufacturing. Before receiving their TIL infusions, patients were given chemotherapy to temporarily deplete their immune system to make room for the new tumor infiltrating lymphocytes.
The overall response rate, meaning the percentage of patients who had a partial or complete response to the therapy, was 31.4%. Also of note, 41.7% of those who responded to the single therapy still had a durable overall response two years or more after receiving the single infusion therapy.
“Our results show that TIL, a therapy that only requires one single infusion of cells, is a viable option for heavily pretreated melanoma patients with advanced disease. We look forward to being able to offer this therapy to more patients in the future,” said Sarnaik.
Iovance is currently in the process of submitted their TIL therapy product, lifiluecel, for U.S. Food and Drug Administration approval. A decision is expected next year.
