Using Adoptive Cell Therapy in the Modern Era of Metastatic Melanoma Treatment

Treatment strategies in metastatic melanoma have attempted to use the immune system to target cancer since the 1980s. Adoptive cell transfer using autologous tumor-infiltrating lymphocytes (TILs) extracted from a patient tumor and cultured in vitro was pioneered in the 1980s and has been developed over the past 30 years through multiple clinical trials. Infusion of ex vivo expanded TILs is performed after completion of nonmyeloablative chemotherapy administered to suppress host regulatory T cells. Systemic interleukin (IL)-2 is administered post-infusion to allow T-cell persistence and activation. Toxicities to treatment are primarily related to pre-infusion chemotherapy and IL-2. Clinical predictors of response to TIL have been assessed but factors have not been elucidated to select patients with high likelihood of response to treatment. Ongoing trials aim to minimize toxicities, guide patient selection, and improve rates and duration of response.