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排序方式: 共有2582条查询结果,搜索用时 312 毫秒
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Kiyotaka Nemoto Tetsuya Shimokawa Masaki Fukunaga Fumio Yamashita Masashi Tamura Hidenaga Yamamori Yuka Yasuda Hirotsugu Azechi Noriko Kudo Yoshiyuki Watanabe Mikio Kido Tsutomu Takahashi Shinsuke Koike Naohiro Okada Yoji Hirano Toshiaki Onitsuka Hidenori Yamasue Michio Suzuki Kiyoto Kasai Ryota Hashimoto Tetsuaki Arai 《Psychiatry and clinical neurosciences》2020,74(1):56-63
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Naohiro Sekiguchi Shinya Rai Wataru Munakata Kenshi Suzuki Hiroshi Handa Hirohiko Shibayama Tomoyuki Endo Yasuhito Terui Noriko Iwaki Noriko Fukuhara Hiro Tatetsu Shinsuke Iida Takayuki Ishikawa Ryota Shiibashi Koji Izutsu 《Cancer science》2020,111(9):3327-3337
Tirabrutinib is a second‐generation Bruton’s tyrosine kinase inhibitor with greater selectivity than ibrutinib. Here, we conducted a multicenter, phase II study of tirabrutinib in patients with treatment‐naïve (Cohort A) or with relapsed/refractory (Cohort B) Waldenström’s macroglobulinemia (WM). Patients were treated with tirabrutinib 480 mg once daily. The primary endpoint was major response rate (MRR; ≥ partial response). Secondary endpoints included overall response rate (ORR; ≥ minor response), time to major response (TTMR), progression‐free survival (PFS), overall survival (OS), and safety. In total, 27 patients (18 in Cohort A; 9 in Cohort B) were enrolled. The median age was 71 y, and the median serum immunoglobulin M level was 3600 mg/dL. Among the patients, 96.2% had the MYD88L265P mutation. MRR and ORR were 88.9% and 96.3%, respectively (Cohort A: MRR, 88.9%; ORR, 94.4%; Cohort B: MRR, 88.9%; ORR, 100%). Median TTMR was 1.87 mo. PFS and OS were not reached with a median follow‐up of 6.5 and 8.3 mo for Cohorts A and B, respectively. The most common adverse events (AEs) were rash (44.4%), neutropenia (25.9%), and leukopenia (22.2%), with most AEs classified as grade 1 or 2. Grade ≥ 3 AEs included neutropenia (11.1%), lymphopenia (11.1%), and leukopenia (7.4%). No grade 5 AEs were noted. All bleeding events were grade 1; none were associated with drug‐related atrial fibrillation or hypertension. Although the follow‐up duration was relatively short, the study met the primary endpoint. Therefore, tirabrutinib monotherapy is considered to be highly effective for both untreated and relapsed/refractory WM with a manageable safety profile. (JapicCTI‐173646). 相似文献
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Tatsuki Ueda Ayako Kumagai Shoichi Iriguchi Yutaka Yasui Tadayo Miyasaka Kengo Nakagoshi Kazuki Nakane Keigo Saito Mari Takahashi Aki Sasaki Shinsuke Yoshida Naoko Takasu Hiroshi Seno Yasushi Uemura Koji Tamada Tetsuya Nakatsura Shin Kaneko 《Cancer science》2020,111(5):1478-1490
The use of allogeneic, pluripotent stem‐cell‐derived immune cells for cancer immunotherapy has been the subject of recent clinical trials. In Japan, investigator‐initiated clinical trials will soon begin for ovarian cancer treatment using human leukocyte antigen (HLA)‐homozygous‐induced pluripotent stem cell (iPSC)‐derived anti–glypican‐3 (GPC3) chimeric antigen receptor (CAR)‐expressing natural killer/innate lymphoid cells (NK/ILC). Using pluripotent stem cells as the source for allogeneic immune cells facilitates stringent quality control of the final product, in terms of efficacy, safety and producibility. In this paper, we describe our methods for the stable, feeder‐free production of CAR‐expressing NK/ILC cells from CAR‐transduced iPSC with clinically relevant scale and materials. The average number of cells that could be differentiated from 1.8‐3.6 × 106 iPSC within 7 weeks was 1.8‐4.0 × 109. These cells showed stable CD45/CD7/CAR expression, effector functions of cytotoxicity and interferon gamma (IFN‐γ) production against GPC3‐expressing tumor cells. When the CAR‐NK/ILC cells were injected into a GPC3‐positive, ovarian‐tumor‐bearing, immunodeficient mouse model, we observed a significant therapeutic effect that prolonged the survival of the animals. When the cells were injected into immunodeficient mice during non–clinical safety tests, no acute systemic toxicity or tumorigenicity of the final product or residual iPSC was observed. In addition, our test results for the CAR‐NK/ILC cells generated with clinical manufacturing standards are encouraging, and these methods should accelerate the development of allogeneic pluripotent stem cell‐based immune cell cancer therapies. 相似文献
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Hironori Tsujimoto Hiroyuki Horiguchi Risa Takahata Satoshi Ono Yoshihisa Yaguchi Shinsuke Nomura Nozomi Ito Manabu Harada Hiromi Nagata Yusuke Ishibashi Keita Kouzu Satoshi Tsuchiya Yujiro Itazaki Seiichiro Fujishima Yoji Kishi Hideki Ueno 《Journal of gastroenterology and hepatology》2020,35(5):788-794
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