Anti-CD40 agonist antibodies: preclinical and clinical experience.
Anti-CD40 agonist antibodies: preclinical and clinical experience.
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DOI：
10.1016/j.uct.2007.06.001
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发表时间：
2007-06-01
期刊：
影响因子：
--
通讯作者：
Vonderheide, Robert H
中科院分区：
文献类型：
--
作者：
Khalil, Magi;Vonderheide, Robert H
细胞表面分子 CD40 是肿瘤坏死因子受体超家族的成员，广泛调节免疫激活并介导肿瘤细胞凋亡。 CD40 由抗原呈递细胞 (APC) 表达，其天然配体与 T 细胞的结合会激活 APC，包括树突状细胞和 B 细胞。在 T 细胞介导的免疫小鼠模型中，激动性 CD40 抗体已被证明可以替代 CD4+ 淋巴细胞提供的 T 细胞帮助。在荷瘤宿主中，CD40 激动剂可引发针对肿瘤相关抗原的有效免疫反应。相比之下，CD40 也在许多肿瘤细胞上表达，并且其在这种情况下的连接介导直接的细胞毒性作用。 CD40 与肿瘤细胞的结合导致体外细胞凋亡和体内肿瘤生长受损。这些观察结果促使人们努力使用激动性 CD40 抗体来治疗癌症患者，并且初步的临床结果令人鼓舞。
The cell-surface molecule CD40, a member of the tumor necrosis factor receptor superfamily, broadly regulates immune activation and mediates tumor apoptosis. CD40 is expressed by antigen-presenting cells (APC) and engagement of its natural ligand on T cells activates APC including dendritic cells and B cells. Agonistic CD40 antibodies have been shown to substitute for T cell help provided by CD4+ lymphocytes in murine models of T cell-mediated immunity. In tumor-bearing hosts, CD40 agonists trigger effective immune responses against tumor-associated antigens. In contrast, CD40 is also expressed on many tumor cells and its ligation in this setting mediates a direct cytotoxic effect. Engagement of CD40 on tumor cells results in apoptosis in vitro and impaired tumor growth in vivo. These observations have prompted efforts to use agonistic CD40 antibodies for the treatment of cancer patients and initial clinical results have been promising.