Snyder Alexandra, Zamarin Dmitriy, Wolchok Jedd D
Prog Tumor Res. 2015;42:22-9. doi: 10.1159/000436998. Epub 2015 Sep 4.
The history of immunotherapy is rooted in the treatment of melanoma and therapy with immune checkpoint-blocking agents is now a cornerstone for the treatment of metastatic melanoma. The first effective immunotherapies approved by the US Food and Drug Administration in melanoma included interleukin-2 for metastatic disease and interferon alpha in the adjuvant setting. These were followed by a group of new therapies, including checkpoint-blocking antibodies targeting cytotoxic T lymphocyte-associated protein 4 and programmed cell death protein 1. Therapies intended to 'reeducate' T cells, such as tumor-infiltrating lymphocyte therapy, oncolytic viruses and tumor vaccines, have yielded promising results and are under development. Finally, the integration of the above therapies as well as development of new coinhibitory and costimulatory agents, though in early stages, appear very promising and likely represent the next phase in drug development for the treatment of metastatic melanoma.
免疫疗法的历史源于黑色素瘤的治疗,而免疫检查点阻断剂疗法如今是转移性黑色素瘤治疗的基石。美国食品药品监督管理局批准的首批用于黑色素瘤治疗的有效免疫疗法包括用于转移性疾病的白细胞介素-2以及辅助治疗中的干扰素α。随后出现了一批新疗法,包括靶向细胞毒性T淋巴细胞相关蛋白4和程序性细胞死亡蛋白1的检查点阻断抗体。旨在“重塑”T细胞的疗法,如肿瘤浸润淋巴细胞疗法、溶瘤病毒和肿瘤疫苗,已取得了有前景的结果,且仍在研发中。最后,上述疗法的整合以及新的共抑制和共刺激剂的开发,尽管尚处于早期阶段,但看起来非常有前景,很可能代表了转移性黑色素瘤治疗药物开发的下一阶段。