Abstract：
Chronic lymphocytic leukaemia (CLL) is a heterogenous disease characterized by the accumulation of neoplastic CD5+/CD19+ B lymphocytes. The spreading of the leukaemia relies on the CLL cell\'s ability to survive in the blood and migrate to and proliferate within the bone marrow and lymphoid tissues. Some patients with CLL are either refractory to the currently available therapies or relapse after treatment; this emphasizes the need for novel therapeutic strategies that improving clinical responses and overcome drug resistance. CD38 is a marker of a poor prognosis and governs a set of survival, proliferation and migration signals that contribute to the pathophysiology of CLL. The literature data evidence a spatiotemporal association between the cell surface expression of CD38 and that of other CLL antigens, such as the B-cell receptor (BCR), CD19, CD26, CD44, the integrin very late antigen 4 (VLA4), the chemokine receptor CXCR4, the vascular endothelial growth factor receptor-2 (VEGF-R2), and the neutrophil gelatinase-associated lipocalin receptor (NGAL-R). Most of these proteins contribute to CLL cell survival, proliferation and trafficking, and cooperate with CD38 in multilayered signal transduction processes. In general, these antigens have already been validated as therapeutic targets in cancer, and a broad repertoire of specific monoclonal antibodies and derivatives are available. Here, we review the state of the art in this field and examine the therapeutic opportunities for cotargeting CD38 and its partners in CLL, e.g. by designing novel bi-/trispecific antibodies.
摘要：
慢性淋巴细胞白血病（CLL）是一种异质性疾病，其特征是肿瘤性CD5/CD19B淋巴细胞的积累。白血病的传播依赖于CLL细胞在血液中存活并迁移到骨髓和淋巴组织中并在其中增殖的能力。一些CLL患者要么对目前可用的疗法难以治疗，要么在治疗后复发；这强调了对改善临床反应并克服耐药性的新型治疗策略的需求。CD38是预后不良的标志，并控制着一组生存，促进CLL病理生理学的增殖和迁移信号。文献数据证明CD38的细胞表面表达与其他CLL抗原的细胞表面表达之间存在时空关联，如B细胞受体（BCR），CD19，CD26，CD44，整合素极晚期抗原4（VLA4），趋化因子受体CXCR4，血管内皮生长因子受体2（VEGF-R2），和中性粒细胞明胶酶相关脂质运载蛋白受体（NGAL-R）。这些蛋白质中的大多数有助于CLL细胞的存活，扩散和贩运，并在多层信号转导过程中与CD38合作。总的来说,这些抗原已经被验证为癌症的治疗靶点，和广泛的特异性单克隆抗体和衍生物是可用的。这里,我们回顾了该领域的最新技术，并研究了联合靶向CD38及其合作伙伴在CLL中的治疗机会，例如通过设计新型双/三特异性抗体。
