肿瘤生物治疗开启黑素瘤临床治疗新时代

Tumor biotherapy: A new era of melanoma treatment

恶性黑素瘤是一类进展快预后差的恶性肿瘤,对传统放化疗均不敏感,晚期患者5年生存率不足5%。随着单克隆抗体、小分子化合物、过继性免疫细胞和溶瘤病毒等生物治疗技术的研发,肿瘤生物治疗为恶性黑素瘤的临床治疗开启了一个新的时代。2011年到2014年,CTLA-4单抗Ipilimumab,PD-1单抗Pembrolizumab、Nivolumab,BRAF抑制剂Vemurafinib、Dabrafinib和MEK抑制剂Trametinib等相继获得FDA批准用于治疗晚期黑素瘤患者,同时多种自体免疫细胞疗法如TIL、CAR-T,以及溶瘤病毒T-VEC等也都在其各自的临床试验中获得了可靠的疗效证据。肿瘤生物治疗以其独特的治疗优势,打破了恶性黑素瘤临床研究近50年的沉寂。然而,我国恶性黑素瘤的生物治疗临床研究尚处于起步阶段,多种生物治疗技术在中国的推广仍需进一步的临床佐证。但随着研究的不断深入,尤其是细胞免疫学、分子生物学和肿瘤遗传学等学科的发展和融合,越来越多的生物治疗方法将逐渐应用于临床,造福于更多的恶性黑素瘤患者。

Malignant melanoma is one of the most aggressive malignant tumors with a 5-year survival rate of less than5% in advanced patients who are highly resistant to traditional radiotherapy and chemotherapy. Nevertheless,significant progress has been made in the treatment of metastatic melanoma in the past five years with the introduction of monoclonal antibodies,small molecule compounds,adoptive cells and oncolytic viruses. To date,monoclonal antibodies against CTLA-4( ipilimumab),PD-1( pembrolizumab and nivolumab) and inhibitors against BRAF( vemurafinib and dabrafinib) or MEK( trametinib) have been approved by the FDA for the treatment of advanced melanoma patients. Moreover,a variety of autoimmune cell therapy methods such as TIL,CAR-T,and oncolytic virus T-VEC have been developed and there therapies have demonstrated clinical benefits in clinical trials. All these tumor biotherapy strategies have broken the silence of clinical research on melanoma. Although further clinical evidence needs to be generated before a wider application of biotherapy technologies in clinical settings in China,melanoma patients will eventually benefit from the integration of cellular immunology,molecular biology and cancer genetics in their fight against the disease.