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Adoptive cell transfer (ACT) using autologous tumor-infiltrating lymphocytes (TIL) is a personalized cell-based immunotherapy developed by the Ella Institute for Melanoma at Sheba Medical Center. The therapeutic process involves surgically harvesting a melanoma lesion from the patient, isolating the naturally occurring T cells that have infiltrated the tumor, and expanding them ex vivo to billions of cells. Prior to reinfusion, patients undergo a lymphodepleting chemotherapy regimen (typically cyclophosphamide and fludarabine) to eliminate immunosuppressive cells and create a favorable environment for the transferred TILs. The expanded cells are then reinfused intravenously alongside high-dose interleukin-2 (IL-2) to support their survival, proliferation, and anti-tumor activity. This therapy is primarily investigated for patients with metastatic or unresectable stage III or IV melanoma, including those who have failed standard treatments. Clinical studies at Sheba have evaluated this TIL therapy both as a monotherapy and in combination with checkpoint inhibitors like ipilimumab to enhance durable response rates.
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