文章：

理解CD30生物学及其治疗靶向：一个提供未来方向洞见的历史视角

Understanding CD30 biology and therapeutic targeting: a historical perspective providing insight into future directions

原文发布日期：2017-09-08

DOI: 10.1038/bcj.2017.85

类型: Review

开放获取: 是

英文摘要：

CD30 is a member of the tumor necrosis factor receptor superfamily. It is characteristically expressed in certain hematopoietic malignancies, including anaplastic large cell lymphoma and Hodgkin lymphoma, among others. The variable expression of CD30 on both normal and malignant lymphoid cells has focused research efforts on understanding the pathogenesis of CD30 upregulation, its contribution to lymphomagenesis through anti-apoptotic mechanisms, and its effect on cell survival. Given the restriction of CD30 to certain tumor types, the logical extension of this has been to attempt to exploit it as a therapeutic target. The efficacy of naked anti-CD30 antibodies in practice was, however, modest. Moreover, combinations with bacterial toxins and radioimmunoconjugates have also had limited success. The development of the antibody-drug compound brentuximab vedotin (BV), however, has rejuvenated interest in CD30 as a tumor target. Phase I and II clinical trials in Hodgkin lymphoma, peripheral T-cell lymphoma, cutaneous T cell lymphoma, and even CD30-expressing B-cell lymphomas, have shown the compound is well tolerated, but more importantly, able to deliver meaningful disease control even in patients with multiply relapsed or refractory disease. FDA approval has been granted for its use in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma. A recent phase III trial of BV in cutaneous T-cell lymphoma has confirmed its superiority to standard of care therapies. In this manuscript, we explore the history of CD30 as a tumor marker and as a therapeutic target, both in the laboratory and in the clinic, with a view to understanding future avenues for further study.

摘要翻译： 

CD30是肿瘤坏死因子受体超家族的一员，其特征性表达见于某些造血系统恶性肿瘤，包括间变性大细胞淋巴瘤、霍奇金淋巴瘤等。CD30在正常及恶性淋巴细胞上的差异性表达，促使研究聚焦于探索CD30上调的发病机制、其通过抗凋亡机制参与淋巴瘤生成的作用以及对细胞存活的影响。鉴于CD30仅局限于特定肿瘤类型表达，其自然延伸研究方向是尝试将其作为治疗靶点。然而实践中，裸抗CD30抗体的疗效较为有限。此外，与细菌毒素及放射免疫结合物的联合疗法亦收效甚微。而抗体-药物复合物brentuximab vedotin（BV）的研发重新激发了CD30作为肿瘤靶点的研究热情。在霍奇金淋巴瘤、外周T细胞淋巴瘤、皮肤T细胞淋巴瘤乃至表达CD30的B细胞淋巴瘤中开展的I期和II期临床试验表明，该化合物不仅耐受性良好，更重要的是即使在多次复发或难治性患者中也能实现有意义的疾病控制。美国FDA已批准其用于复发型霍奇金淋巴瘤和系统性间变性大细胞淋巴瘤。近期一项针对皮肤T细胞淋巴瘤的BVIII期临床试验证实了其优于标准治疗方案。本文通过回顾CD30在实验室与临床中作为肿瘤标志物及治疗靶点的研究历程，旨在为未来深入研究探索方向。

原文链接：

Understanding CD30 biology and therapeutic targeting: a historical perspective providing insight into future directions