Antitumor Activity Associated with Prolonged Persistence of Adoptively Transferred NY-ESO-1 (c259)T Cells in Synovial Sarcoma.
Antitumor Activity Associated with Prolonged Persistence of Adoptively Transferred NY-ESO-1 (c259)T Cells in Synovial Sarcoma.
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DOI：
10.1158/2159-8290.cd-17-1417
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发表时间：
2018-08
期刊：
影响因子：
28.2
通讯作者：
Mackall CL
中科院分区：
文献类型：
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作者：
D'Angelo SP;Melchiori L;Merchant MS;Bernstein D;Glod J;Kaplan R;Grupp S;Tap WD;Chagin K;Binder GK;Basu S;Lowther DE;Wang R;Bath N;Tipping A;Betts G;Ramachandran I;Navenot JM;Zhang H;Wells DK;Van Winkle E;Kari G;Trivedi T;Holdich T;Pandite L;Amado R;Mackall CL
我们评估了表达NY-ESO-1c 259的自体T细胞（NY-ESO-1c 259 T细胞）在转移性滑膜肉瘤患者中的安全性和活性，NY-ESO-1c 259是一种识别HLA-A2限制性NY-ESO-1/LAGE 1a衍生肽的亲和力增强型T细胞受体（TCR）。50%的患者（6/12）发生了确认的抗肿瘤反应，其特征为数月内肿瘤缩小。循环NY-ESO-1c 259 T细胞在所有患者中存在于输注后，并且在所有应答者中持续至少6个月。大多数输注的NY-ESO-1c 259 T细胞在离体扩增后表现出效应记忆表型，但持续的库主要包括中央记忆和干细胞记忆亚群，这些亚群保持多功能，尽管有持续的肿瘤负荷，但没有显示T细胞耗竭的证据。对CD 8 + NY-ESO-1c 259 T细胞中内源性TCR的下一代测序揭示了克隆多样性，而没有随时间收缩。这些数据表明，NY-ESO-1c 259 T细胞的再生池产生了持续的效应细胞供应，以介导持续的、有临床意义的抗肿瘤作用。
We evaluated the safety and activity of autologous T cells expressing NY-ESO-1c259, an affi nity-enhanced T-cell receptor (TCR) recognizing an HLA-A2–restricted NY-ESO-1/LAGE1a—derived peptide, in patients with metastatic synovial sarcoma (NY-ESO-1c259T cells). Confi rmed antitumor responses occurred in 50% of patients (6/12) and were characterized by tumor shrinkage over several months. Circulating NY-ESO-1c259T cells were present postinfusion in all patients and persisted for at least 6 months in all responders. Most of the infused NY-ESO-1c259T cells exhibited an effector memory phenotype following ex vivo expansion, but the persisting pools comprised largely central memory and stem-cell memory subsets, which remained polyfunctional and showed no evidence of T-cell exhaustion despite persistent tumor burdens. Next-generation sequencing of endogenous TCRs in CD8+ NY-ESO-1c259T cells revealed clonal diversity without contraction over time. These data suggest that regenerative pools of NY-ESO-1c259T cells produced a continuing supply of effector cells to mediate sustained, clinically meaningful antitumor effects.