Treatment of multiple myeloma with adoptively transferred chimeric NKG2D receptor-expressing T cells.
Treatment of multiple myeloma with adoptively transferred chimeric NKG2D receptor-expressing T cells.
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作者：
多发性骨髓瘤约占所有血液恶性肿瘤的10%。我们之前已经证明，表达嵌合NKG 2D受体（chNKG 2D）的人T细胞分泌促炎细胞因子并杀死人骨髓瘤细胞，嵌合NKG 2D受体（chNKG 2D）由融合至CD 3 β胞质结构域的NKG 2D组成。在这项研究中，我们显示chNKG 2D T细胞在多发性骨髓瘤小鼠模型中是有效的。用一次或两次chNKG 2D T细胞输注处理具有已建立的5 T33 MM-GFP肿瘤的小鼠。与用表达wtNKG 2D的T细胞处理的小鼠相比，单次给予chNKG 2D T细胞可延长存活期，其中半数chNKG 2D T细胞处理的小鼠长期存活。两次输注chNKG 2D T细胞导致所有小鼠的无肿瘤存活。静脉注射后，ChNKG 2D T细胞位于肿瘤生长部位，包括骨髓和脾脏。chNKG 2D T细胞注射后，肿瘤部位的活化宿主T细胞和NK细胞以及血清IFNγ增加。存活的小鼠能够抵抗5 T33 MM细胞的再攻击，但不能抵抗RMA淋巴瘤细胞，这表明小鼠产生了保护性的特异性记忆反应。这些数据表明，chNKG 2D T细胞可能是多发性骨髓瘤的有效过继细胞疗法。
Multiple myeloma causes approximately 10% of all hematologic malignancies. We have previously shown that human T cells expressing chimeric NKG2D receptors (chNKG2D) consisting of NKG2D fused to the CD3ζ cytoplasmic domain secrete proinflammatory cytokines and kill human myeloma cells. In this study, we show chNKG2D T cells are effective in a murine model of multiple myeloma. Mice with established 5T33MM-GFP tumors were treated with one or two infusions of chNKG2D T cells. Compared to mice treated with T cells expressing wtNKG2D, a single dose of chNKG2D T cells increased survival, with half of the chNKG2D T cell-treated mice surviving long-term. Two infusions of chNKG2D T cells led to tumor-free survival in all mice. ChNKG2D T cells were located at sites of tumor growth, including the bone marrow and spleen after i.v. injection. There was an increase in activated host T cells and NK cells at tumor sites and in serum IFNγ after chNKG2D T cell injection. Surviving mice were able to resist a rechallenge with 5T33MM cells but not RMA lymphoma cells, indicating that the mice developed a protective, specific memory response. These data demonstrate that chNKG2D T cells may be an effective adoptive cellular therapy for multiple myeloma.
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影响因子：
8.8
作者：
Manning, L S;Berger, J D;O'Donoghue, H L;Sheridan, G N;Claringbold, P G;Turner, J H
通讯作者：
Turner, J H
通过淋巴结消除来清除稳态细胞因子下沉，增强了采用转移的肿瘤特异性CD8+ T细胞的功效。
影响因子：
15.3
作者：
Gattinoni, Luca;Finkelstein, Steven E;Klebanoff, Christopher A;Antony, Paul A;Palmer, Douglas C;Spiess, Paul J;Hwang, Leroy N;Yu, Zhiya;Wrzesinski, Claudia;Heimann, David M;Surh, Charles D;Rosenberg, Steven A;Restifo, Nicholas P
通讯作者：
Restifo, Nicholas P
DOI：
10.4049/jimmunol.0900721
发表时间：
2009-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Barber A;Sentman CL
通讯作者：
Sentman CL
影响因子：
4.4
作者：
Barber, Amorette;Zhang, Tong;Sentman, Charles L.
通讯作者：
Sentman, Charles L.
影响因子：
2.6
作者：
Alici, Evren;Konstantinidis, Kyriakos V.;Dilber, M. Sirac
通讯作者：
Dilber, M. Sirac