单细胞追踪揭示黑色素瘤 TIL 治疗过程中肿瘤反应性 T 细胞的可塑性
Single-cell tracking reveals tumor-reactive T cell plasticity during melanoma TIL therapy.
TIL(肿瘤浸润淋巴细胞)过继细胞治疗可在转移性黑色素瘤中诱导持久缓解,然而在体外扩增过程中及回输后,调控肿瘤反应性T细胞命运的克隆和转录动态仍知之甚少。
英文原题:Tumour-infiltrating lymphocyte therapy comes of age in the era of genetic engineering.
在两项独立的里程碑式临床试验之后,TIL 疗法于 2024 年获批,已确立该方案为一种可行的治疗选择,在难治性黑色素瘤中缓解率高达 50%。
从免疫检查点调节到TIL(肿瘤浸润淋巴细胞)过继细胞转移,癌症免疫治疗的进展显著改善了晚期癌症患者,尤其是转移性黑色素瘤患者的结局。两项独立里程碑式临床试验后,TIL疗法于2024年获批,确立了其作为可行治疗选择的地位,在耐药性黑色素瘤中的应答率最高可达50%。基因工程为进一步提升TIL疗效和持久性带来了新机会,包括利用病毒载体过表达细胞因子或嵌合受体,以及使用CRISPR-Cas9等非病毒基因组编辑技术敲除PD-1和CISH等抑制性基因。本综述概述基因工程化TIL的现状,重点介绍临床前进展和正在开展的临床试验。随着这些工程化产品进入临床评估,预计其将扩展个体化免疫治疗工具,并改善更广泛实体瘤的持久治疗结局。
Advances in cancer immunotherapy from immune checkpoint modulation to adoptive cell transfer of tumour-infiltrating lymphocytes (TILs) have greatly improved outcomes for patients with advanced cancers, particularly metastatic melanoma. The approval of TIL therapy in 2024 following two independent landmark clinical trials has established this approach as a viable treatment option, with response rates of up to 50% in treatment-resistant melanoma. Genetic engineering offers new opportunities to further improve TIL efficacy and durability, including viral vector-mediated overexpression of cytokines or chimeric receptors, and non-viral genome editing techniques such as CRISPR-Cas9 to delete inhibitory genes such as PD-1 and CISH. In this Review we outline the current state of genetically engineered TILs, highlighting both preclinical advances and ongoing clinical trials. As these engineered products are evaluated in clinical settings, they are expected to expand the personalised immunotherapy toolkit and improve durable outcomes across a broader range of solid tumours.
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