Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients.
Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients.
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自体肿瘤浸润淋巴细胞和低剂量白细胞介素-2的过养细胞疗法在转移性黑色素瘤患者中。
DOI：
10.1186/1479-5876-10-169
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发表时间：
2012-08-21
影响因子：
7.4
通讯作者：
Svane IM
中科院分区：
文献类型：
--
作者：
Ellebaek E;Iversen TZ;Junker N;Donia M;Engell-Noerregaard L;Met Ö;Hölmich LR;Andersen RS;Hadrup SR;Andersen MH;thor Straten P;Svane IM
诱导性细胞疗法可以基于肿瘤特异性T细胞（例如自体肿瘤浸润淋巴细胞（TIL））的分离、体外活化和扩增以及在化疗诱导的淋巴细胞耗竭后将这些细胞再输注到患者中。与高剂量白细胞介素（IL）-2一起，这种治疗已被给予晚期恶性黑色素瘤患者，并观察到令人印象深刻的反应率，但也观察到显著的IL-2相关毒性。在这里，我们提供了来自丹麦转化研究中心的一项可行性研究的数据，该研究使用TIL过继转移联合低剂量皮下IL-2注射。这是一项初步试验（ClinicalTrials.gov标识符：NCT 00937625），纳入转移性黑色素瘤患者，PS ≤ 1，年龄<70岁，可测量和进展性疾病，未累及中枢神经系统。6例患者接受淋巴细胞清除化疗、TIL输注和14天皮下低剂量IL-2注射（2 MIU/天）治疗。低剂量IL-2显著降低了治疗相关的毒性，没有3 - 4级IL-2相关的不良事件。6例治疗患者中有2例观察到客观临床缓解，持续完全缓解（30+和10+个月），2例患者病情稳定（4和5个月），2例患者在治疗后不久发生进展。分析治疗前后输注细胞和外周血淋巴细胞的肿瘤反应性。输注产品中肿瘤特异性T细胞的绝对数量倾向于与临床应答相关，并且在1例完全缓解患者中观察到外周肿瘤反应性T细胞的诱导。在用过继细胞疗法与低剂量IL-2组合治疗后诱导了完全和持久的应答，这显著降低了该疗法的毒性。
Adoptive cell therapy may be based on isolation of tumor-specific T cells, e.g. autologous tumor infiltrating lymphocytes (TIL), in vitro activation and expansion and the reinfusion of these cells into patients upon chemotherapy induced lymphodepletion. Together with high-dose interleukin (IL)-2 this treatment has been given to patients with advanced malignant melanoma and impressive response rates but also significant IL-2 associated toxicity have been observed. Here we present data from a feasibility study at a Danish Translational Research Center using TIL adoptive transfer in combination with low-dose subcutaneous IL-2 injections. This is a pilot trial (ClinicalTrials.gov identifier: NCT00937625) including patients with metastatic melanoma, PS ≤1, age <70, measurable and progressive disease and no involvement of the central nervous system. Six patients were treated with lymphodepleting chemotherapy, TIL infusion, and 14 days of subcutaneous low-dose IL-2 injections, 2 MIU/day. Low-dose IL-2 considerably decreased the treatment related toxicity with no grade 3–4 IL-2 related adverse events. Objective clinical responses were seen in 2 of 6 treated patients with ongoing complete responses (30+ and 10+ months), 2 patients had stable disease (4 and 5 months) and 2 patients progressed shortly after treatment. Tumor-reactivity of the infused cells and peripheral lymphocytes before and after therapy were analyzed. Absolute number of tumor specific T cells in the infusion product tended to correlate with clinical response and also, an induction of peripheral tumor reactive T cells was observed for 1 patient in complete remission. Complete and durable responses were induced after treatment with adoptive cell therapy in combination with low-dose IL-2 which significantly decreased toxicity of this therapy.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
3.9
作者：
Dudley, ME;Wunderlich, JR;Rosenberg, SA
通讯作者：
Rosenberg, SA
影响因子：
11.5
作者：
Besser, Michal J.;Shapira-Frommer, Ronnie;Schachter, Jacob
通讯作者：
Schachter, Jacob
影响因子：
7.2
作者：
Kvistborg P;Shu CJ;Heemskerk B;Fankhauser M;Thrue CA;Toebes M;van Rooij N;Linnemann C;van Buuren MM;Urbanus JH;Beltman JB;Thor Straten P;Li YF;Robbins PF;Besser MJ;Schachter J;Kenter GG;Dudley ME;Rosenberg SA;Haanen JB;Hadrup SR;Schumacher TN
通讯作者：
Schumacher TN
影响因子：
1.1
作者：
Junker N;Thor Straten P;Andersen MH;Svane IM
通讯作者：
Svane IM