Phase I study of chimeric antigen receptor modified T cells in treating HER2-positive advanced biliary tract cancers and pancreatic cancers.
Phase I study of chimeric antigen receptor modified T cells in treating HER2-positive advanced biliary tract cancers and pancreatic cancers.
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嵌合抗原受体修饰 T 细胞治疗 HER2 阳性晚期胆道癌和胰腺癌的 I 期研究。
DOI：
10.1007/s13238-017-0440-4
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发表时间：
2018-10
期刊：
影响因子：
21.1
通讯作者：
Han W
中科院分区：
文献类型：
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作者：
Feng K;Liu Y;Guo Y;Qiu J;Wu Z;Dai H;Yang Q;Wang Y;Han W
本项I期临床试验（NCT 01935843）旨在评价靶向人表皮生长因子受体2（HER 2）的嵌合抗原受体工程化T细胞（CART）免疫疗法在晚期胆道癌（BTC）和胰腺癌（PC）患者中的安全性、可行性和活性。具有HER 2阳性（>50%）BTC和PC的合格患者入组试验。在由白蛋白结合型紫杉醇（100-200 mg/m2）和环磷酰胺（15-35 mg/kg）组成的预处理后，输注培养良好的CART-HER 2细胞。连续测量外周血中的CAR转基因拷贝数以监测CART-HER 2细胞在体内的扩增和持久性。11例入组患者接受了1至2个周期的CART-HER 2细胞输注（中位CAR+ T细胞2.1 × 106/kg）。预处理导致轻度至中度疲乏、恶心/呕吐、肌痛/关节痛和淋巴细胞减少症。除1例3级急性发热综合征和1例转氨酶异常升高（>9 ULN）外，与CART-HER 2细胞输注相关的不良事件均为轻度至中度。输注后毒性包括1例可逆性重度上消化道出血，发生在CART-HER 2细胞输注后11天胃窦被转移侵袭的患者中，以及2例1-2级迟发性发热，伴有C反应蛋白和白细胞介素-6的释放。所有患者的临床反应评估均可评价，其中1例获得了4.5个月的部分反应，5例获得了疾病稳定。中位无进展生存期为4.8个月（范围1.5-8.3个月）。最后，这项研究的数据证明了CART-HER 2免疫疗法的安全性和可行性，并显示了令人鼓舞的临床活性信号。
This phase I clinical trial (NCT01935843) is to evaluate the safety, feasibility, and activity of chimeric antigen receptor-engineered T cell (CART) immunotherapy targeting human epidermal growth factor receptor 2 (HER2) in patients with advanced biliary tract cancers (BTCs) and pancreatic cancers (PCs). Eligible patients with HER2-positive (>50%) BTCs and PCs were enrolled in the trial. Well cultured CART-HER2 cells were infused following the conditioning treatment composed of nab-paclitaxel (100–200 mg/m2) and cyclophosphamide (15–35 mg/kg). CAR transgene copy number in the peripheral blood was serially measured to monitor the expansion and persistence of CART-HER2 cells in vivo. Eleven enrolled patients received 1 to 2-cycle CART-HER2 cell infusion (median CAR+ T cell 2.1 × 106/kg). The conditioning treatment resulted in mild-to-moderate fatigue, nausea/vomiting, myalgia/arthralgia, and lymphopenia. Except one grade-3 acute febrile syndrome and one abnormal elevation of transaminase (>9 ULN), adverse events related to the infusion of CART-HER2 cells were mild-to-moderate. Post-infusion toxicities included one case of reversible severe upper gastrointestinal hemorrhage which occurred in a patient with gastric antrum invaded by metastasis 11 days after the CART-HER2 cell infusion, and 2 cases of grade 1–2 delayed fever, accompanied by the release of C-reactive protein and interleukin-6. All patients were evaluable for assessment of clinical response, among which 1 obtained a 4.5-months partial response and 5 achieved stable disease. The median progression free survival was 4.8 months (range, 1.5–8.3 months). Finally, data from this study demonstrated the safety and feasibility of CART-HER2 immunotherapy, and showed encouraging signals of clinical activity.
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影响因子：
--
作者：
Nam AR;Kim JW;Cha Y;Ha H;Park JE;Bang JH;Jin MH;Lee KH;Kim TY;Han SW;Im SA;Kim TY;Oh DY;Bang YJ
通讯作者：
Bang YJ
影响因子：
82.9
作者：
Klebanoff CA;Rosenberg SA;Restifo NP
通讯作者：
Restifo NP
影响因子：
45.3
作者：
Ahmed, Nabil;Brawley, Vita S.;Gottschalk, Stephen
通讯作者：
Gottschalk, Stephen
影响因子：
64.8
作者：
Cho, HS;Mason, K;Leahy, DJ
通讯作者：
Leahy, DJ
表达 CD19 嵌合抗原受体的自体或供体来源的 T 细胞在患有髓外白血病的成人 B-ALL 中的耐受性和疗效。
影响因子：
7.2
作者：
Dai H;Zhang W;Li X;Han Q;Guo Y;Zhang Y;Wang Y;Wang C;Shi F;Zhang Y;Chen M;Feng K;Wang Q;Zhu H;Fu X;Li S;Han W
通讯作者：
Han W