The recent approval by the U.S. Food and Drug Administration of lifileucel, the first commercial tumor-infiltrating lymphocyte (TIL) therapy for advanced melanoma, marks a significant advancement in cancer treatment. In a new commentary published in Cancer Cell, scientists at Moffitt Cancer Center provide a comprehensive overview of the therapy’s development and highlight its transformative potential.
“TIL therapy represents a major advance in personalized cancer care and offers new possibilities for patients with treatment-resistant cancers,” said Amod Sarnaik, MD, senior author and senior member of Moffitt’s Department of Cutaneous Oncology.
Tumor-infiltrating lymphocyte therapy has been in development for several decades. Preclinical studies to evaluate its efficacy began at the National Cancer Institute (NCI) in the early 1980s. James J. Mulé, IPh.D., a renowned immunologist and associate director of Moffitt’s Translational Sciences Center, brought TIL research to the cancer center in 2003. Since then, Moffitt has played a pivotal role in the development and validation of immunotherapy.
In 2010, Moffitt initiated its first TIL trials, the first site outside of NCI to treat patients with the investigational therapy. This initial study, which treated 13 patients with advanced metastatic melanoma, yielded promising results: five responses, including two complete responses lasting more than five years. The commentary examines Moffitt’s subsequent clinical trials, which aimed to address the high discontinuation rate due to disease progression during TIL manufacturing. These trials combined TIL therapy with newly approved anti-melanoma agents, significantly reducing the discontinuation rate from 32% to 5%.
Moffitt is also working on the next generation of TIL therapies. Dr. Shari Pilon-Thomas and other immunologists at the center are investigating innovative ways to stimulate and enhance the growth and production of TIL therapy and determining the best timing of infusion to ensure optimal patient outcomes. Moffitt researchers are also expanding this therapeutic approach to treat other types of solid tumor cancers, including lung, sarcoma, cervical and bladder cancer.
“We are beginning to realize the potential of T-cell and cell-based therapies to treat advanced cancers. The FDA approval of lifileucel is a monumental step toward inspiring further investment and innovation in T-cell therapies, particularly TIL therapy,” said Moffitt President and CEO Dr. Patrick Hwu. “Our pioneering research at Moffitt on next-generation TIL therapies aims to extend these life-saving treatments to a broader range of cancer patients.”