靶向CD30治疗经典霍奇金淋巴瘤的研究进展

Advances in Targeting CD30 for Classic Hodgkin Lymphoma Therapy

CD30属于肿瘤坏死因子受体超家族的一员,是一种定位在细胞膜上的I型跨膜蛋白质。正常情况下CD30仅在部分活化的B淋巴细胞和T淋巴细胞中表达,参与维持机体免疫系统的功能。值得注意的是,CD30在多种淋巴瘤亚群,尤其是经典霍奇金淋巴瘤(classical Hodgkin’s lymphoma,cHL)中高表达。高表达的CD30可通过多种机制影响cHL的进展,例如激活NF-κB、MAPK-ERK信号通路,影响肿瘤微环境等促进c HL肿瘤细胞的增殖和抗凋亡能力。CD30是cHL进展的重要驱动分子,结合它在cHL肿瘤细胞膜上特异性高表达,因此CD30是一个极具潜力的治疗cHL的靶点。CD30抗体偶联药物维布妥昔单抗已被批准用于复发难治性cHL的临床治疗,其临床适应症不断扩大,显著改善了cHL患者的预后。此外,有多项研究正在尝试开发其他靶向CD30(例如CD30单抗、CD30 CAR-T细胞等)治疗cHL的方法,部分临床前研究以及临床试验展示出令人振奋的疗效。该文将综述CD30在cHL中的表达、功能以及靶向CD30治疗cHL的研究进展。

CD30,a member of TNFR(tumor necrosis factor receptor)superfamily,is a type I transmembrane protein that is localized to cell membrane.CD30 is only expressed in some activated B lymphocytes and T lymphocytes and involved in regulating the function of immune system.However,it is upregulated in a variety of lymphomas,especially in cHL(classical Hodgkin’s lymphoma).Highly expressed CD30 promotes cHL progression through various mechanisms,such as activation of NF-κB,MAPK-ERK signaling pathway,and influence of tumor microenvironment to promote the proliferation and anti-apoptosis of cHL tumor cells.As it is highly overexpressed in cHL tumors and promotes disease progression,CD30 is a promising therapeutic target for cHL.BV(Brentuximab vedotin),a kind of CD30 related antibody-drug conjugate,has been approved for the clinical treatment of relapsed/refractory cHL.The clinical indications of BV have been rapidly expanded and significantly improved the prognosis of cHL patients.In addition to BV,several studies are working to develop other CD30-targeted therapies for cHL,such as CD30 monoclonal antibodies and CD30 CAR-T cells.The effectiveness of these treatments has confirmed by many preclinical studies and clinical trials.This review will summarize the expression and function of CD30 in cHL and cover the advances in targeting CD30 for cHL.