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:Engineered T cell therapy for viral and non-viral epithelial cancers.
工程化T细胞疗法在血液系统恶性肿瘤中显示出显著疗效,并具有应用于常见上皮癌的潜力。
工程化T细胞疗法在血液系统恶性肿瘤中已显示出显著疗效,并具有应用于常见上皮癌的潜力。多种T细胞治疗策略,包括TIL(肿瘤浸润淋巴细胞)的过继转移、嵌合抗原受体(CAR)-T细胞和T细胞受体(TCR)-T细胞,已在临床试验中进行了研究。近期研究已确立使用TCR-T细胞治疗人乳头瘤病毒(HPV)相关癌症作为上皮癌原理验证研究的模型。这些研究及其他研究为肿瘤消退机制、治疗靶点、治疗安全性、治疗设计以及常见类型癌症治愈性细胞疗法的障碍提供了关键见解。本视角将回顾并整合从临床试验中使用细胞和基因疗法治疗病毒性和非病毒性上皮癌所获得的认知,并将探讨过往经验如何指导未来治疗和生物标志物发现的策略。
Engineered T cell therapy has shown remarkable efficacy in hematologic malignancies and has the potential for application to common epithelial cancers. Diverse T cell therapy strategies including adoptive transfer of tumor-infiltrating lymphocytes, chimeric antigen receptor (CAR)-T cells, and T cell receptor (TCR)-T cells have been studied in clinical trials. Recent research has established treatment of human papillomavirus (HPV)-associated cancers with TCR-T cells as a model for proof-of-principle studies in epithelial cancers. These studies and others have provided critical insight into mechanisms of tumor regression, therapeutic targets, treatment safety, treatment design, and barriers to curative cell therapies for common types of cancer. This perspective will review and consolidate understanding gained from clinical trials to treat viral and non-viral epithelial cancers with cell and gene therapy and will examine how past experience may guide future strategy in treatment and biomarker discovery.
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