CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors.
The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors.
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睾丸生殖细胞肿瘤(TGCTs)是预后非常好的癌症,即使在转移性情况下也是如此,其高治愈潜力主要归因于以顺铂为基础的化疗的应用。
然而,约15%的患者会发展为铂类难治性疾病并经历多次复发。因此,对于具有更好疗效和最小长期副作用的新型治疗药物存在未满足的需求。免疫治疗药物开发的最新进展,特别是免疫检查点抑制剂(ICIs),为在各种肿瘤类型(包括GCTs)中测试其活性提供了机会。本综述旨在分析这些肿瘤的免疫微环境,并呈现最近测试针对GCTs的免疫治疗药物的研究数据。现有知识的大部分来自病例报告或小型队列研究,特别是涉及PD-1/PD-L1轴的ICIs单独使用或与抗CTLA-4单克隆抗体联合使用的研究。其他免疫治疗靶向方法,包括抗体-药物偶联物、抗体前药、疫苗、酪氨酸激酶抑制剂、嵌合抗原受体(CAR)T细胞疗法,具有生物学依据,已显示出初步活性或目前正在测试中。关于这些方法及其他方法的日益增多的证据将有助于拓宽目前针对铂类难治性TGCTs的有限治疗手段。
Testicular germ cell tumors (TGCTs) are cancers with very good prognosis, even in the metastatic setting, with high curative potential mainly attributed to the introduction of cisplatin-based chemotherapy.
However, approximately 15% of the patients develop platinum-refractory disease and suffer multiple relapses.
Therefore, there is an unmet need for novel therapeutic agents with improved efficacy and minimal long-term side effects. Recent advances in the development of immunotherapeutic agents, particularly immune checkpoint inhibitors (ICIs), have offered an opportunity to test their activity in various tumor types, including GCTs. This review aims to analyze the immune microenvironment of these tumors and present the most recently available data from studies that have tested immunotherapeutic agents against GCTs.
The majority of the available knowledge derives from case reports or small cohort studies, particularly those involving ICIs of the PD-1/PD-L1 axis alone or in combination with anti-CTLA-4 monoclonal antibodies.
Other immunotherapeutic targeted approaches, including antibody-drug conjugates, antibody prodrugs, vaccines, tyrosine kinase inhibitors, chimeric antigen receptor (CAR) T-cell therapy, have biological rationales and have shown preliminary activity or are currently being tested. Growing evidence on these and other approaches will assist in broadening the currently limited treatment armamentarium against platinum-refractory TGCTs.
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