Merhavi-Shoham Efrat, Itzhaki Orit, Markel Gal, Schachter Jacob, Besser Michal J
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.
Cancer J. 2017 Jan/Feb;23(1):48-53. doi: 10.1097/PPO.0000000000000240.
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.
肿瘤浸润淋巴细胞（TILs）的过继性细胞疗法（ACT）是一种强大的免疫疗法，可诱导持久的完全缓解，显著延长黑色素瘤患者的生存期。突变衍生的新抗原最近被确定为TILs识别和排斥肿瘤的关键因素。针对新抗原的T细胞受体（TCR）基因的分离及其重新转导至外周T细胞可能会提供一种新的ACT形式。嵌合抗原受体（CAR）对T细胞进行基因改造已在血液系统恶性肿瘤中取得了显著的临床效果，但迄今为止在实体瘤中的效果较差。黑色素瘤方面的相关报道非常有限。CAR T细胞工程的进展，包括抑制信号的中和或额外的安全开关，可能也会为黑色素瘤治疗带来机会。我们综述了TILs、T细胞受体和CAR修饰的T细胞过继性疗法的临床结果和最新进展，并讨论了黑色素瘤治疗的未来方向。
