Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial.
Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: a phase 1 trial.
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DOI：
10.1038/s41591-021-01462-y
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发表时间：
2021-08
期刊：
影响因子：
82.9
通讯作者：
Antonia SJ
中科院分区：
文献类型：
--
作者：
Creelan BC;Wang C;Teer JK;Toloza EM;Yao J;Kim S;Landin AM;Mullinax JE;Saller JJ;Saltos AN;Noyes DR;Montoya LB;Curry W;Pilon-Thomas SA;Chiappori AA;Tanvetyanon T;Kaye FJ;Thompson ZJ;Yoder SJ;Fang B;Koomen JM;Sarnaik AA;Chen DT;Conejo-Garcia JR;Haura EB;Antonia SJ
使用肿瘤浸润淋巴细胞（TIL）的连续性细胞疗法已在黑色素瘤中显示出活性，但先前尚未在转移性非小细胞肺癌（NSCLC）中进行评估。我们进行了一项单臂开放标签I期试验（NCT 03215810），在20例接受nivolumab单药治疗后出现初始进展的晚期NSCLC患者中进行nivolumab联合TIL给药。主要终点是安全性，次要终点包括客观缓解率、缓解持续时间和T细胞持久性。自体TIL从用IL-2培养的切碎的肿瘤离体扩增。患者接受环磷酰胺和氟达拉滨淋巴细胞清除、TIL输注和白细胞介素-2，随后接受纳武单抗维持治疗。根据预先规定的重度毒性发生率≤17%的标准（95%置信区间，3-29%），符合安全性终点。在13例可评价患者中，3例确认缓解，11例肿瘤负荷减轻，中位最佳变化为35%。两名患者在1.5年后获得完全缓解。在探索性分析中，我们发现识别多种类型癌症突变的T细胞在TIL治疗后被检测到，并且在应答患者中富集。治疗后外周血中新抗原反应性T细胞克隆型增加并持续存在。自体TIL的细胞治疗通常是安全和临床活性的，并且可能构成转移性肺癌的新治疗策略。
Adoptive cell therapy using tumor infiltrating lymphocytes (TIL) has shown activity in melanoma, but has not been previously evaluated in metastatic non-small cell lung cancer (NSCLC). We conducted a single-arm open-label phase 1 trial (NCT03215810) of TIL administered with nivolumab in 20 patients with advanced NSCLC following initial progression on nivolumab monotherapy. The primary endpoint was safety, and secondary endpoints included objective response rate, duration of response, and T-cell persistence. Autologous TIL was expanded ex vivo from minced tumors cultured with IL-2. Patients received cyclophosphamide and fludarabine lymphodepletion, TIL infusion, and interleukin-2, followed by maintenance nivolumab. The endpoint of safety was met according to the pre-specified criteria of ≤17% rate of severe toxicity (95% confidence interval, 3–29%). Of 13 evaluable patients, 3 had confirmed responses and 11 had reduction in tumor burden, with a median best change of 35%. Two patients achieved complete responses ongoing 1.5 years later. In exploratory analyses, we found T cells recognizing multiple types of cancer mutations were detected after TIL treatment, and were enriched in responding patients. Neoantigen-reactive T cell clonotypes increased and persisted in the peripheral blood after treatment. Cell therapy with autologous TIL is generally safe and clinically active, and may constitute a new treatment strategy in metastatic lung cancer.
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影响因子：
12.4
作者：
Haas, Andrew R.;Tanyi, Janos L.;Beatty, Gregory L.
通讯作者：
Beatty, Gregory L.
DOI：
10.4049/jimmunol.1700893
发表时间：
2017-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jurtz V;Paul S;Andreatta M;Marcatili P;Peters B;Nielsen M
通讯作者：
Nielsen M
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
28.2
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
通讯作者：
Mackall CL
影响因子：
6.2
作者：
Doebele RC;Lu X;Sumey C;Maxson DA;Weickhardt AJ;Oton AB;Bunn PA Jr;Barón AE;Franklin WA;Aisner DL;Varella-Garcia M;Camidge DR
通讯作者：
Camidge DR