Clinical and immunologic evaluation of three metastatic melanoma patients treated with autologous melanoma-reactive TCR-transduced T cells.
Clinical and immunologic evaluation of three metastatic melanoma patients treated with autologous melanoma-reactive TCR-transduced T cells.
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DOI：
10.1007/s00262-017-2073-0
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Nishimura MI
中科院分区：
文献类型：
--
作者：
Moore T;Wagner CR;Scurti GM;Hutchens KA;Godellas C;Clark AL;Kolawole EM;Hellman LM;Singh NK;Huyke FA;Wang SY;Calabrese KM;Embree HD;Orentas R;Shirai K;Dellacecca E;Garrett-Mayer E;Li M;Eby JM;Stiff PJ;Evavold BD;Baker BM;Le Poole IC;Dropulic B;Clark JI;Nishimura MI
30多年来，恶性黑色素瘤的发病率一直在增加，尽管有新的治疗方法，但转移性疾病仍然难以治疗。我们描述了过继细胞治疗的I期临床试验（NCT01586403）的初步结果，其中三名患者接受了用慢病毒转导的自体CD4+和CD8+ T细胞，慢病毒携带酪氨酸酶特异性TCR和标记蛋白，截断CD34 （CD34t）。这种不寻常的MHC i类限制性TCR在CD4+和CD8+ T细胞中产生功能性反应。在转导的T细胞上监测的参数包括活化（CD25, CD69），抑制（PD-1, TIM-3, CTLA-4），共刺激（OX40）和记忆（CCR7）标记。在临床试验中，T细胞被激活、转导、选择为CD34t+细胞，然后在IL-2和IL-15中被重新激活和扩增。在淋巴细胞耗尽化疗后，患者给予转导T细胞和IL-2，并随访临床和生物学反应。在观察期间（42,523和255天），在三名接受治疗的患者的循环中检测到转导的T细胞。患者1对输注耐受良好，但6周后因疾病进展而死亡。根据RECIST标准，患者2有部分缓解，然后进展。进展后，患者2被给予高剂量IL-2，随后达到完全缓解，与白癜风的发展一致。患者3有混合反应，不符合RECIST临床反应标准，并发展为白癜风。在这三例患者中的两例中，酪氨酸酶反应性tcr转导T细胞过继转移到转移性黑色素瘤患者中具有临床和/或生物活性，未发生严重不良事件。
Malignant melanoma incidence has been increasing for over 30 years, and despite promising new therapies, metastatic disease remains difficult to treat. We describe preliminary results from a Phase I clinical trial (NCT01586403) of adoptive cell therapy in which three patients received autologous CD4+ and CD8+ T cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a marker protein, truncated CD34 (CD34t). This unusual MHC Class I-restricted TCR produces functional responses in both CD4+ and CD8+ T cells. Parameters monitored on transduced T cells included activation (CD25, CD69), inhibitory (PD-1, TIM-3, CTLA-4), costimulatory (OX40), and memory (CCR7) markers. For the clinical trial, T cells were activated, transduced, selected for CD34t+ cells, then re-activated and expanded in IL-2 and IL-15. After lymphodepleting chemotherapy, patients were given transduced T cells and IL-2 and were followed for clinical and biological responses. Transduced T cells were detected in the circulation of three treated patients for the duration of observation (42, 523, and 255 days). Patient 1 tolerated the infusion well but died from progressive disease after six weeks. Patient 2 had a partial response by RECIST criteria then progressed. After progressing, Patient 2 was given high-dose IL-2 and subsequently achieved complete remission, coinciding with the development of vitiligo. Patient 3 had a mixed response that did not meet RECIST criteria for a clinical response and developed vitiligo. In two of these three patients, adoptive transfer of tyrosinase-reactive TCR-transduced T cells into metastatic melanoma patients had clinical and/or biological activity without serious adverse events.
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影响因子：
5.8
作者：
June, Carl H.;Maus, Marcela V.;Plesa, Gabriela;Johnson, Laura A.;Zhao, Yangbing;Levine, Bruce L.;Grupp, Stephan A.;Porter, David L.
通讯作者：
Porter, David L.
影响因子：
15.9
作者：
Baitsch, Lukas;Baumgaertner, Petra;Speiser, Daniel E.
通讯作者：
Speiser, Daniel E.
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。
影响因子：
7.4
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
通讯作者：
Svane IM
使用全局分析来扩展与T细胞受体及其肽/MHC配体的结合测量的准确性和精度。
影响因子：
5
作者：
Blevins SJ;Baker BM
通讯作者：
Baker BM
DOI：
10.1097/cji.0b013e3181fad2b0
发表时间：
2010-11
期刊：
Journal of immunotherapy (Hagerstown, Md. : 1997)
影响因子：
--
作者：
Inozume T;Hanada K;Wang QJ;Ahmadzadeh M;Wunderlich JR;Rosenberg SA;Yang JC
通讯作者：
Yang JC