Constitutive and TNFα-inducible expression of chondroitin sulfate proteoglycan 4 in glioblastoma and neurospheres: Implications for CAR-T cell therapy.
Constitutive and TNFα-inducible expression of chondroitin sulfate proteoglycan 4 in glioblastoma and neurospheres: Implications for CAR-T cell therapy.
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DOI：
10.1126/scitranslmed.aao2731
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发表时间：
2018-02-28
影响因子：
17.1
通讯作者：
Dotti G
中科院分区：
文献类型：
--
作者：
Pellegatta S;Savoldo B;Di Ianni N;Corbetta C;Chen Y;Patané M;Sun C;Pollo B;Ferrone S;DiMeco F;Finocchiaro G;Dotti G
肿瘤相关抗原的异质性表达限制了嵌合抗原受体（CAR）重定向T细胞（CAR-T）治疗胶质母细胞瘤（GBM）的功效。我们发现硫酸软骨素蛋白聚糖4（CSPG 4）在67%的GBM标本中高度表达，异质性有限。CSPG 4还在体外生长为神经球（GBM-NS）的原代GBM衍生细胞上表达，其概括了原代GBM的组织病理学和分子特征。CSPG 4.CAR-Ts在颅内肿瘤接种后在体外和体内有效地控制GBM-NS的生长。此外，CSPG 4.CAR-Ts也有效对抗具有中等至低CSPG 4表达的GBM-NS。这种作用是通过肿瘤周围小胶质细胞释放的肿瘤坏死因子-α（TNFα）诱导CSPG 4在体内上调肿瘤细胞介导的。总体而言，GBM中CSPG 4的组成型和TNFα诱导型表达可大大降低靶向抗原在肿瘤细胞上异质表达时观察到的肿瘤细胞逃逸风险。
The heterogeneous expression of tumor-associated antigens limits the efficacy of chimeric antigen receptor (CAR)–redirected T cells (CAR-Ts) for the treatment of glioblastoma (GBM). We have found that chondroitin sulfate proteoglycan 4 (CSPG4) is highly expressed in 67% of the GBM specimens with limited heterogeneity. CSPG4 is also expressed on primary GBM-derived cells, grown in vitro as neurospheres (GBM-NS), which recapitulate the histopathology and molecular characteristics of primary GBM. CSPG4.CAR-Ts efficiently controlled the growth of GBM-NS in vitro and in vivo upon intracranial tumor inoculation. Moreover, CSPG4.CAR-Ts were also effective against GBM-NS with moderate to low expression of CSPG4. This effect was mediated by the in vivo up-regulation of CSPG4 on tumor cells, induced by tumor necrosis factor–α (TNFα) released by the microglia surrounding the tumor. Overall, the constitutive and TNFα-inducible expression of CSPG4 in GBM may greatly reduce the risk of tumor cell escape observed when targeted antigens are heterogeneously expressed on tumor cells.
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影响因子：
11.2
作者：
Brown CE;Starr R;Martinez C;Aguilar B;D'Apuzzo M;Todorov I;Shih CC;Badie B;Hudecek M;Riddell SR;Jensen MC
通讯作者：
Jensen MC
LY6C+“炎症单核细胞”是在西尼罗河病毒脑炎中以致病方式募集的小胶质前体。
DOI：
10.1084/jem.20080421
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Getts DR;Terry RL;Getts MT;Müller M;Rana S;Shrestha B;Radford J;Van Rooijen N;Campbell IL;King NJ
通讯作者：
King NJ
第三代EGFRVIII特异性嵌合抗原受体的脑内递送有效地针对人神经胶质瘤。
影响因子：
2
作者：
Choi, Bryan D.;Suryadevara, Carter M.;Gedeon, Patrick C.;Herndon, James E., II;Sanchez-Perez, Luis;Bigner, Darell D.;Sampson, John H.
通讯作者：
Sampson, John H.
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：
5.7
作者：
Coniglio, Salvatore J.;Eugenin, Eliseo;Segall, Jeffrey E.
通讯作者：
Segall, Jeffrey E.