免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumor-Infiltrating Lymphocyte Therapy in Melanoma: Facts to the Future.
Tumor-Infiltrating Lymphocyte Therapy in Melanoma: Facts to the Future.
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TIL(肿瘤浸润淋巴细胞)过继细胞治疗势头渐起,并在晚期黑色素瘤患者中显示出持久应答。尽管日益被视为部分黑色素瘤患者的治疗选择,TIL治疗尚未获任何监管机构批准。现代黑色素瘤疗法出现之前开展的早期TIL研究已显示临床疗效;对有应答患者,中位总生存期可超过20个月,表现出显著的长期生存。TIL治疗是一个多步骤过程:从肿瘤中获取患者特异性的肿瘤驻留T细胞,体外扩增后,在给予淋巴细胞清除预处理后回输给同一患者,并随后给予支持性IL-2。对于经过多线治疗的转移性黑色素瘤患者,包括已接受现代免疫检查点抑制剂和BRAF靶向药后进展者(这是未满足医疗需求较高的人群),客观缓解率一直为30%–50%。现代TIL疗法已取得重要进展,目前正探索优化患者选择、改进TIL生产和提高疗效的策略。本文综述TIL疗法治疗黑色素瘤及其他实体瘤的发展历程、当前经验、挑战、实践考量和未来方向。
Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) is gaining momentum and demonstrating durable responses in patients with advanced melanoma. Although increasingly considered as a treatment option for select patients with melanoma, TIL therapy is not yet approved by any regulatory agency. Pioneering studies with first-generation TIL therapy, undertaken before the advent of modern melanoma therapeutics, demonstrated clinical efficacy and remarkable long-term overall survival, reaching beyond 20 months for responding patients.
TIL therapy is a multistep process of harvesting patient-specific tumor-resident T cells from tumors, ex vivo T-cell expansion, and re-infusion into the same patient after a lymphodepleting preparative regimen, with subsequent supportive IL2 administration.
Objective response rates between 30% and 50% have consistently been observed in heavily pretreated patients with metastatic melanoma, including those who have progressed after modern immune checkpoint inhibitors and BRAF targeted agents, a population with high unmet medical need. Although significant strides have been made in modern TIL therapeutics, refinement strategies to optimize patient selection, enhance TIL production, and improve efficacy are being explored.
Here, we review past and present experience, current challenges, practical considerations, and future aspirations in the evolution of TIL therapy for the treatment of melanoma as well as other solid tumors.
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