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葡萄膜黑色素瘤免疫治疗的最新进展与挑战

Recent Advances and Challenges in Uveal Melanoma Immunotherapy.

作者信息

Fu Yihang, Xiao Wei, Mao Yuxiang

机构信息

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.

Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China.

出版信息

Cancers (Basel). 2022 Jun 23;14(13):3094. doi: 10.3390/cancers14133094.

Abstract

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Compared to cutaneous melanoma (CM), which mainly harbors or mutations, UM predominantly harbors or mutations. Although primary UM can be controlled locally, approximately 50% of patients still develop metastases. To date, there have been no standard therapeutic strategies for the prevention or treatment of metastases. Unfortunately, chemotherapy and targeted therapies only induce minimal responses in patients with metastatic UM, with a median survival time of only 4-5 months after metastasis detection. Immunotherapy agents, such as immune checkpoint inhibitors, have achieved pioneering outcomes in CM but have shown limited effects in UM. Researchers have explored several feasible checkpoints to identify options for future therapies. Cancer vaccines have shown little in the way of therapeutic benefit in patients with UM, and there are few ongoing trials providing favorable evidence, but adoptive cell transfer-related therapies seem promising and deserve further investigation. More recently, the immune-mobilizing monoclonal T-cell receptor against the cancer molecule tebentafusp showed impressive antitumor effects. Meanwhile, oncolytic viruses and small molecule inhibitors have also gained ground. This review highlights recent progress in burgeoning treatments and provides innovative insights on feasible strategies for the treatment of UM.

摘要

葡萄膜黑色素瘤(UM)是成人中最常见的原发性眼内恶性肿瘤。与主要携带 或 突变的皮肤黑色素瘤(CM)相比,UM主要携带 或 突变。尽管原发性UM可以通过局部控制,但仍有大约50%的患者会发生转移。迄今为止,尚无预防或治疗转移的标准治疗策略。不幸的是,化疗和靶向治疗仅能使转移性UM患者产生极小的反应,转移检测后中位生存时间仅为4至5个月。免疫治疗药物,如免疫检查点抑制剂,在CM中取得了开创性成果,但在UM中效果有限。研究人员已经探索了几个可行的检查点,以确定未来治疗的选择。癌症疫苗在UM患者中几乎没有显示出治疗益处,目前正在进行的试验很少能提供有利证据,但过继性细胞转移相关疗法似乎很有前景,值得进一步研究。最近,针对癌症分子替贝福司的免疫动员单克隆T细胞受体显示出令人印象深刻的抗肿瘤效果。同时,溶瘤病毒和小分子抑制剂也取得了进展。本综述强调了新兴治疗方法的最新进展,并为UM治疗的可行策略提供了创新性见解。

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