Tetramer guided, cell sorter assisted production of clinical grade autologous NY-ESO-1 specific CD8(+) T cells.
Tetramer guided, cell sorter assisted production of clinical grade autologous NY-ESO-1 specific CD8(+) T cells.
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DOI：
10.1186/s40425-014-0036-y
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发表时间：
2014
影响因子：
10.9
通讯作者：
Yee C
中科院分区：
文献类型：
--
作者：
Pollack SM;Jones RL;Farrar EA;Lai IP;Lee SM;Cao J;Pillarisetty VG;Hoch BL;Gullett A;Bleakley M;Conrad EU 3rd;Eary JF;Shibuya KC;Warren EH;Carstens JN;Heimfeld S;Riddell SR;Yee C
免疫性T细胞疗法代表了治疗癌症患者的有吸引力的方式。外周血单核细胞已被用作抗原特异性T细胞的来源，但识别通常表达的抗原如NY-ESO-1的T细胞的频率非常低，限制了这种方法对其他实体瘤的适用性。为了克服这一点，我们测试了一种策略，该策略将体外刺激期间的IL-21调节与首次使用四聚体引导的细胞分选相结合，以产生NY-ESO-1特异性细胞毒性T淋巴细胞（CTL）。在临床生产条件下，在6例NY-ESO-1阳性肉瘤患者中评价CTL生成，并表征其表型和功能特性。体外刺激后，用NY-ESO-1四聚体染色的T细胞在单次通过临床级分选器后从低至0.4%的频率富集至>90%。NY-ESO-1特异性T细胞由所有6名患者产生。最终产物平均扩增1200倍至总共360亿个细胞，是寡克隆的，并且含有67-97%的具有识别内源性NY-ESO-1的记忆表型的CD 8+、四聚体+ T细胞。这项研究代表了使用四聚体引导的细胞分选来产生用于过继治疗的T细胞的第一个系列。当用于靶向更广泛表达的肿瘤抗原如WT-1和其他癌症-睾丸抗原时，这种方法将增强过继性T细胞治疗的范围和可行性。本文的在线版本（doi：10.1186/s40425-014-0036-y）包含补充材料，可供授权用户使用。
Adoptive T cell therapy represents an attractive modality for the treatment of patients with cancer. Peripheral blood mononuclear cells have been used as a source of antigen specific T cells but the very low frequency of T cells recognizing commonly expressed antigens such as NY-ESO-1 limit the applicability of this approach to other solid tumors. To overcome this, we tested a strategy combining IL-21 modulation during in vitro stimulation with first-in-class use of tetramer-guided cell sorting to generate NY-ESO-1 specific cytotoxic T lymphocytes (CTL). CTL generation was evaluated in 6 patients with NY-ESO-1 positive sarcomas, under clinical manufacturing conditions and characterized for phenotypic and functional properties. Following in vitro stimulation, T cells stained with NY-ESO-1 tetramer were enriched from frequencies as low as 0.4% to >90% after single pass through a clinical grade sorter. NY-ESO-1 specific T cells were generated from all 6 patients. The final products expanded on average 1200-fold to a total of 36 billion cells, were oligoclonal and contained 67-97% CD8+, tetramer+ T cells with a memory phenotype that recognized endogenous NY-ESO-1. This study represents the first series using tetramer-guided cell sorting to generate T cells for adoptive therapy. This approach, when used to target more broadly expressed tumor antigens such as WT-1 and additional Cancer-Testis antigens will enhance the scope and feasibility of adoptive T cell therapy. The online version of this article (doi:10.1186/s40425-014-0036-y) contains supplementary material, which is available to authorized users.
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影响因子：
56.9
作者：
Morgan, Richard A.;Dudley, Mark E.;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.
DOI：
10.1038/nri3191
发表时间：
2012-03-22
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Restifo NP;Dudley ME;Rosenberg SA
通讯作者：
Rosenberg SA
影响因子：
17.1
作者：
Brentjens RJ;Davila ML;Riviere I;Park J;Wang X;Cowell LG;Bartido S;Stefanski J;Taylor C;Olszewska M;Borquez-Ojeda O;Qu J;Wasielewska T;He Q;Bernal Y;Rijo IV;Hedvat C;Kobos R;Curran K;Steinherz P;Jurcic J;Rosenblat T;Maslak P;Frattini M;Sadelain M
通讯作者：
Sadelain M
影响因子：
158.5
作者：
Hunder, Naomi N.;Wallen, Herschel;Yee, Cassian
通讯作者：
Yee, Cassian
影响因子：
9.7
作者：
Kawai, A;Naito, N;Beppu, Y
通讯作者：
Beppu, Y