PDF(Pubmed)
Abstract：
Cancerous B cells are almost indistinguishable from their non-malignant counterparts regarding their surface antigen expression. Accordingly, the challenge to be faced consists in elimination of the malignant B cell population while maintaining a functional adaptive immune system. Here, we present an IgM-specific antibody-drug conjugate masked by fusion of the epitope-bearing IgM constant domain. Antibody masking impaired interaction with soluble pentameric as well as cell surface-expressed IgM molecules rendering the antibody cytotoxically inactive. Binding capacity of the anti-IgM antibody drug conjugate was restored upon conditional protease-mediated demasking which consequently enabled target-dependent antibody internalization and subsequent induction of apoptosis in malignant B cells. This easily adaptable approach potentially provides a novel mechanism of clonal B cell lymphoma eradication to the arsenal available for non-Hodgkin\'s lymphoma treatment.
摘要：
就其表面抗原表达而言,癌性B细胞与它们的非恶性对应物几乎无法区分。因此，面临的挑战在于消除恶性B细胞群,同时维持功能性适应性免疫系统.这里,我们提出了一种IgM特异性抗体-药物偶联物,该偶联物被携带表位的IgM恒定结构域融合所掩盖.抗体掩蔽与可溶性五聚体以及细胞表面表达的IgM分子的相互作用受损,使得抗体细胞毒性失活。抗IgM抗体药物缀合物的结合能力在条件性蛋白酶介导的去掩蔽后恢复,这因此使得靶依赖性抗体内化和随后在恶性B细胞中诱导凋亡。这种易于适应的方法可能为非霍奇金淋巴瘤治疗提供了一种新的克隆性B细胞淋巴瘤根除机制。
