Department of Neuroscience, Alfred Centre, 99 Commercial Road, Melbourne, VIC 3004, Australia.
Department of Neuroscience, Alfred Centre, 99 Commercial Road, Melbourne, VIC 3004, Australia; Department of Neurology, Alfred Health, 55 Commercial Rd, Melbourne, VIC, 3004, Australia.
Mult Scler Relat Disord. 2021 Jul;52:102962. doi: 10.1016/j.msard.2021.102962. Epub 2021 Apr 15.
Cladribine is an approved selective immune reconstitution therapy for relapsing-remitting MS (RRMS). It was first developed and used to treat various forms of cancer, particularly leukemia via parenteral administration. The oral tablet version of cladribine was later developed to treat RRMS, an autoimmune disorder of the central nervous system (CNS) with periods of relapse and remission. Cladribine is found to selectively deplete adaptive immune cell types, and its role on innate immune cells is largely unknown. Among the lymphocyte populations and subtypes, the magnitude and kinetics of depletion by cladribine vary substantially. The current consensus on the selective cytotoxic effect of cladribine is that it is dependent on the deoxycytidine kinase (DCK) to 5'nucleotidase (5-NT) ratio of the immune cell type. Nonetheless, there are some discrepancies that cannot be fully elucidated by the DCK:5-NT ratio paradigm. This review aims to delineate the development and pharmacological properties of cladribine, and elucidate its influence on lymphoid and myeloid cells in MS.
克拉屈滨是一种已获批的、用于治疗复发缓解型多发性硬化症（RRMS）的选择性免疫重建疗法。它最初是通过注射给药被开发并用于治疗各种形式的癌症，尤其是白血病。后来，克拉屈滨的口服片剂版本被开发出来，用于治疗 RRMS，这是一种中枢神经系统（CNS）的自身免疫性疾病，具有复发和缓解期。克拉屈滨被发现可选择性耗竭适应性免疫细胞类型，但其对固有免疫细胞的作用在很大程度上尚不清楚。在淋巴细胞群体和亚群中，克拉屈滨的耗竭幅度和动力学有很大差异。目前关于克拉屈滨选择性细胞毒性作用的共识是，它依赖于免疫细胞类型的脱氧胞苷激酶（DCK）与 5'-核苷酸酶（5-NT）的比值。尽管如此，仍有一些差异无法完全用 DCK：5-NT 比值范式来解释。本综述旨在描述克拉屈滨的开发和药理学特性，并阐明其对 MS 中淋巴样和髓样细胞的影响。
