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Brentuxinmab vedotin,单用或联合 bendamustine 治疗自然杀伤 T 细胞淋巴瘤

英文原题:Brentuxinmab vedotin, alone or combine with bendamustine in the treatment of natural killer T cell lymphoma.

PubMed 2022/07/14(内容时间) Hematol Oncol Q1 · IF 4.1(JCR 2025)

研究概要

本研究为BV用于治疗NKTCL的可能性提供了参考,既可作为单一药物,也可与苯达莫司汀联合使用。

中文摘要

自然杀伤(NK)/T细胞淋巴瘤是侵袭性很强的非霍奇金淋巴瘤亚型。自然杀伤/T细胞淋巴瘤(NKTCL)患者预后仍然较差,亟需更有效的治疗策略改善复发或难治性(R/R)患者的生存。约40%的NK/T细胞淋巴瘤可见CD30表达。维布妥昔单抗(BV)是一种靶向CD30的抗体偶联药物,其抗体连接单甲基澳瑞他汀E,可杀伤癌细胞。既往研究显示,BV联合苯达莫司汀治疗霍奇金淋巴瘤疗效较好。本研究在体外和体内评估BV单药及其联合苯达莫司汀治疗NKTCL的效果。研究者检测了6种NKTCL细胞系的CD30表达水平,发现BV对淋巴瘤细胞的抑制效率与CD30表达相关。BV联合苯达莫司汀对NKTCL细胞具有协同作用。联合治疗在体内外均协同抑制细胞增殖并增强细胞凋亡;两药还协同使NKTCL细胞系停滞于G2/M期,并协同造成DNA损伤。本研究为BV单药或联合苯达莫司汀治疗NKTCL提供了潜在应用依据。

展开英文摘要原文

Natural killer (NK)/T cell lymphoma is a highly aggressive subtype of non-Hodgkin lymphoma. The prognosis of patients with natural killer T cell lymphoma (NKTCL) remains poor. More potent treatment strategies are urgently needed to improve the survival of these patients with R/R NKTCL. CD30 expression has been reported to occur in about 40% of NK/T cell lymphoma. Brentuximab vedotin (BV), a monomethyl auristatin E conjugated CD30 antibody, targets CD30 to kill cancer cells. Therapeutic combination of BV and bendamustine has been shown to be highly effective in Hodgkin lymphoma. We investigated efficacy of BV in treating NKTCL as a single therapy, and in combination with bendamustine in vitro and in vivo. We determined CD30 expression levels in 6 NKTCL cell lines. The efficiency of lymphoma cell inhibition by BV correlates with CD30 expression. We also determined the efficacy of BV in combination with bendamustine and found synergistic effects with bendamustine in NKTCL. Combined BV and bendamustine treatment exerted synergistic antiproliferation effect and enhanced cell apoptotic in vitro and in vivo. Brentuximab vedotin and bendamustine synergistically arrested cell cycle at the G2/M phase in NKTCL cell lines. The combination of BV and bendamustine was demonstrated to synergistically damage DNA in NKTCL. This study provides a reference for possible application on using BV for the treatment of NKTCL, either as a single agent or in combination with bendamustine.

论文信息

作者
Zhang P、Shi C、Song Y、Li Z、Zhang M、Jin M
单位
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.China
期刊
Hematological oncology2022 Dec
原文标识
PubMed 35797410 · DOI 10.1002/hon.3042