通过靶向肿瘤相关巨噬细胞的嵌合受体工程化溶瘤病毒重振内源性抗肿瘤免疫
Rejuvenating endogenous antitumor immunity via a chimeric receptor-engineered oncolytic virus targeting tumor-associated macrophages.
肿瘤细胞治疗研究
英文原题:Recent Advances and Challenges in Uveal Melanoma Immunotherapy.
Recent Advances and Challenges in Uveal Melanoma Immunotherapy.
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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 BRAF 或 NRAS 突变的皮肤黑色素瘤(CM)相比,UM 主要携带 GNAQ 或 GNA11 突变。尽管原发性 UM 可以在局部得到控制,但仍有约 50% 的患者发生转移。迄今为止,尚无预防或治疗转移的标准治疗策略。遗憾的是,化疗和靶向治疗对转移性 UM 患者仅能诱导极小的缓解,转移检出后的中位生存时间仅为 4-5 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。研究人员已探索了若干可行的检查点,以寻找未来治疗的选项。癌症疫苗在 UM 患者中显示出的治疗获益甚微,且很少有正在进行的试验提供有利证据,但过继性细胞转移相关疗法似乎前景可观,值得进一步研究。最近,针对癌症分子 tebentafusp 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。本综述重点介绍了新兴治疗的最新进展,并为 UM 的可行治疗策略提供了创新性见解。
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Compared to cutaneous melanoma (CM), which mainly harbors BRAF or NRAS mutations, UM predominantly harbors GNAQ or GNA11 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.
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