title: Adoptive Cell Therapy for Metastatic Melanoma.
abstract: Adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TILs) is a powerful form of immunotherapy by inducing durable complete responses that significantly extend the survival of melanoma patients. Mutation-derived neoantigens were recently identified as key factors for tumor recognition and rejection by TILs. The isolation of T-cell receptor (TCR) genes directed against neoantigens and their retransduction into peripheral T cells may provide a new form of ACT.Genetic modifications of T cells with chimeric antigen receptors (CARs) have demonstrated remarkable clinical results in hematologic malignancies, but are so far less effective in solid tumors. Only very limited reports exist in melanoma. Progress in CAR T-cell engineering, including neutralization of inhibitory signals or additional safety switches, may open opportunities also in melanoma.We review clinical results and latest developments of adoptive therapies with TILs, T-cell receptor, and CAR-modified T cells and discuss future directions for the treatment of melanoma.
authors.affiliation: From the *Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Tel Hashomer; and †Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Merhavi-Shoham
authors.forename: Orit
authors.initials: O
authors.lastname: Itzhaki
authors.forename: Gal
authors.initials: G
authors.lastname: Markel
authors.forename: Jacob
authors.initials: J
authors.lastname: Schachter
authors.forename: Michal J
authors.initials: MJ
authors.lastname: Besser
mesh_terms: D000818:Animals; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic