DNAM-1-based chimeric antigen receptors enhance T cell effector function and exhibit in vivo efficacy against melanoma.
DNAM-1-based chimeric antigen receptors enhance T cell effector function and exhibit in vivo efficacy against melanoma.
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DOI：
10.1007/s00262-014-1648-2
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发表时间：
2015-04
影响因子：
5.8
通讯作者：
Sentman, Charles L.
中科院分区：
文献类型：
--
作者：
Wu, Ming-Ru;Zhang, Tong;Alcon, Andre;Sentman, Charles L.
嵌合抗原受体（CAR） T细胞疗法在治疗癌症方面具有巨大的潜力，因此需要能够靶向多种肿瘤类型并具有靶向非血液系统恶性肿瘤潜力的新型CAR。在这项研究中，利用自然杀伤细胞激活受体DNAM-1的肿瘤识别能力来设计靶向多种肿瘤类型的car。DNAM-1配体、PVR和nectin-2在原发性人类白血病、骨髓瘤、卵巢癌、黑色素瘤、神经母细胞瘤和尤因肉瘤中表达。DNAM-1 CARs在体外表现出较高的肿瘤细胞毒性，但IFN-γ分泌较低。与其他CAR设计相比，共刺激结构域并没有改善DNAM-1 CAR的表达和功能。DNAM-1/CD3zeta CAR在小鼠黑色素瘤模型中降低了肿瘤负荷。总之，基于dnam -1的car可能具有治疗PVR和表达nectin-2的血液学和实体肿瘤的潜力。
Chimeric antigen receptor (CAR) T cell therapies hold great potential for treating cancers, and new CARs that can target multiple tumor types and have the potential to target non-hematological malignancies are needed. In this study, the tumor recognition ability of a natural killer cell-activating receptor, DNAM-1 was harnessed to design CARs that target multiple tumor types. DNAM-1 ligands, PVR and nectin-2, are expressed on primary human leukemia, myeloma, ovarian cancer, melanoma, neuroblastoma, and Ewing sarcoma. DNAM-1 CARs exhibit high tumor cell cytotoxicity but low IFN-γ secretion in vitro. In contrast to other CAR designs, co-stimulatory domains did not improve the expression and function of DNAM-1 CARs. A DNAM-1/CD3zeta CAR reduced tumor burden in a murine melanoma model in vivo. In conclusion, DNAM-1-based CARs may have the potential to treat PVR and nectin-2 expressing hematological and solid tumors.
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DOI：
10.1158/1078-0432.ccr-10-0735
发表时间：
2010-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cho D;Shook DR;Shimasaki N;Chang YH;Fujisaki H;Campana D
通讯作者：
Campana D
影响因子：
17.1
作者：
Fedorov VD;Themeli M;Sadelain M
通讯作者：
Sadelain M
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：
4.4
作者：
Dardalhon, V;Schubart, AS;Kuchroo, VK
通讯作者：
Kuchroo, VK
DOI：
10.1083/jcb.200501090
发表时间：
2005-10-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fujito T;Ikeda W;Kakunaga S;Minami Y;Kajita M;Sakamoto Y;Monden M;Takai Y
通讯作者：
Takai Y