CD30 targeting with brentuximab vedotin: a novel therapeutic approach to primary effusion lymphoma
CD30 targeting with brentuximab vedotin: a novel therapeutic approach to primary effusion lymphoma
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DOI：
10.1182/blood-2013-01-481713
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发表时间：
2013-08-15
期刊：
影响因子：
20.3
通讯作者：
Lossos, Izidore S.
中科院分区：
文献类型：
--
作者：
Bhatt, Shruti;Ashlock, Brittany M.;Lossos, Izidore S.
原发性渗出性淋巴瘤(PEL)是非霍奇金淋巴瘤的一种侵袭性亚型，目前的治疗方法具有生存期短的特点，迫切需要开发新的治疗方法。Brentuximab vedotin(SGN-35)是一种抗CD30的单抗(CAC10)，它与微管干扰剂单甲基金葡胺偶联，是治疗复发的表达CD30的经典霍奇金淋巴瘤和系统性间变性大细胞淋巴瘤的有效药物。在这里，我们证明了PEL细胞株和原发肿瘤表达CD30，因此可能成为布妥昔单抗维多丁治疗的潜在靶点。在体外，布妥昔单抗维多丁抑制细胞增殖，诱导细胞周期停滞，并触发PEL细胞系的凋亡。此外，在体内，Brentuximab vedotin促进了先前报道的UM-PEL-1肿瘤和UM-PEL-3肿瘤小鼠的肿瘤消退和延长存活时间，这些肿瘤来自一种新建立的具有Kaposi肉瘤相关疱疹病毒和Epstein-Barr病毒阳性的PEL细胞系。总体而言，我们的研究结果首次表明，布妥昔单抗维多丁可以作为治疗PEL的有效方法，并为评估布妥昔单抗维多丁在PEL患者临床研究中的应用提供了强有力的临床前适应证。
Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma characterized by short survival with current therapies, emphasizing the urgent need to develop new therapeutic approaches. Brentuximab vedotin (SGN-35) is an anti-CD30 monoclonal antibody (cAC10) conjugated by a protease-cleavable linker to a microtubuledisrupting agent, monomethyl auristatin E. Brentuximab vedotin is an effective treatment of relapsed CD30-expressing Classical Hodgkin and systemic anaplastic large cell lymphomas. Herein, we demonstrated that PEL cell lines and primary tumors express CD30 and thus may serve as potential targets for brentuximab vedotin therapy. In vitro treatment with brentuximab vedotin decreased cell proliferation, induced cell cycle arrest, and triggered apoptosis of PEL cell lines. Furthermore, in vivo brentuximab vedotin promoted tumor regression and prolonged survival of mice bearing previously reported UM-PEL-1 tumors as well as UM-PEL-3 tumors derived from a newly established and characterized Kaposi's sarcoma-associated herpesvirus-and Epstein-Barr virus-positive PEL cell line. Overall, our results demonstrate for the first time that brentuximab vedotinmay serve as an effective therapy for PEL and provide strong preclinical indications for evaluation of brentuximab vedotin in clinical studies of PEL patients.