Brentuxinmab vedotin, alone or combine with bendamustine in the treatment of natural killer T cell lymphoma
Brentuxinmab vedotin, alone or combine with bendamustine in the treatment of natural killer T cell lymphoma
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DOI：
10.1002/hon.3042
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发表时间：
2022-07
影响因子：
3.3
通讯作者：
Ping Zhang;C. Shi;Yue Song;Zhaoming Li;Mingzhi Zhang;M. Jin
中科院分区：
文献类型：
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作者：
Ping Zhang;C. Shi;Yue Song;Zhaoming Li;Mingzhi Zhang;M. Jin
自然杀伤(NK)/T细胞淋巴瘤是一种高度侵袭性的非霍奇金淋巴瘤亚型。自然杀伤T细胞淋巴瘤(NKTCL)患者预后较差。迫切需要更有效的治疗策略来提高这些R/R NKTCL患者的存活率。据报道，CD30在约40%的NK/T细胞淋巴瘤中表达。Brentuximab vedotin(BV)是一种单甲基金葡胺E偶联CD30抗体，靶向CD30杀死癌细胞。BV和苯达莫司汀的联合治疗已被证明对霍奇金淋巴瘤非常有效。我们研究了BV单独治疗NKTCL以及与苯达莫司汀联合治疗NKTCL的疗效。我们检测了6个NKTCL细胞系中CD30的表达水平。BV对淋巴瘤细胞的抑制作用与CD30的表达有关。我们还检测了BV与苯达莫司汀联合治疗NKTCL的疗效，并发现了与苯达莫司汀的协同作用。BV与苯达莫司汀联合应用，在体内外具有协同抗增殖和促进细胞凋亡的作用。布妥昔单抗和苯达莫司汀协同作用使NKTCL细胞周期停滞于G2/M期。BV与苯达莫司汀联合应用对NKTCL细胞DNA有协同损伤作用。本研究为BV单独或与苯达莫司汀合用治疗NKTCL提供了参考。
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.