Anti-CD38 Antibody Therapy: Windows of Opportunity Yielded by the Functional Characteristics of the Target Molecule
Anti-CD38 Antibody Therapy: Windows of Opportunity Yielded by the Functional Characteristics of the Target Molecule
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DOI：
10.2119/molmed.2013.00009
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发表时间：
2013-01-01
影响因子：
5.7
通讯作者：
Malavasi, Fabio
中科院分区：
文献类型：
--
作者：
Chillemi, Antonella;Zaccarello, Gianluca;Malavasi, Fabio
单克隆抗体（mAb）的体内使用已经成为治疗各种人类疾病的常规临床实践的支柱。根据所治疗的病症，许多分子可以作为靶点。目前进入人体临床试验，CD38分子是一个特别有吸引力的目标，因为它独特的表达模式和它的双重作用，受体和胞外酶。本文综述了抗CD38单克隆抗体治疗的最新进展和面临的挑战。我们提出了一个概要的CD 38的证据，特别是在骨髓瘤和慢性淋巴细胞白血病（CLL）。我们的目标是使基础科学的数据对不同的临床受众有帮助和可访问性，同时提高其体内使用的潜力。所涵盖的主题包括组织分布和单克隆抗体连接的信号实现，以及通过利用有关分子调节的信息与批准用于体内使用的药物相结合来增加靶细胞上细胞密度的可能性。还分析了CD38作为酶的行为：CD38是导致肿瘤微环境中腺苷产生的途径的组分，从而诱导局部无反应性。因此，CD38不仅可能是mAb介导治疗的主要靶点，而且其功能性阻断可能有助于癌症免疫治疗和结局的总体改善。
In vivo use of monoclonal antibodies (mAbs) has become a mainstay of routine clinical practice in the treatment of various human diseases. A number of molecules can serve as targets, according to the condition being treated. Now entering human clinical trials, CD38 molecule is a particularly attractive target because of its peculiar pattern of expression and its twin role as receptor and ectoenzyme. This review provides a range of analytical perspectives on the current progress in and challenges to anti-CD38 mAb therapy. We present a synopsis of the evidence available on CD38, particularly in myeloma and chronic lymphocytic leukemia (CLL). Our aim is to make the data from basic science helpful and accessible to a diverse clinical audience and, at the same time, to improve its potential for in vivo use. The topics covered include tissue distribution and signal implementation by mAb ligation and the possibility of increasing cell density on target cells by exploiting information about the molecule's regulation in combination with drugs approved for in vivo use. Also analyzed is the behavior of CD38 as an enzyme: CD38 is a component of a pathway leading to the production of adenosine in the tumor microenvironment, thus inducing local anergy. Consequently, not only might CD38 be a prime target for mAb-mediated therapy, but its functional block may contribute to general improvement in cancer immunotherapy and outcomes.