Multimeric Biotherapeutics, Inc., La Jolla, CA, USA.
Int Rev Immunol. 2012 Aug;31(4):279-88. doi: 10.3109/08830185.2012.703272.
CD40 stimulation has produced impressive results in early-stage clinical trials of patients with cancer. Further progress will be facilitated by a better understanding of how the CD40 receptor becomes activated and the subsequent functions of CD40-stimulated immune cells. This review focuses on two aspects of this subject. The first is the recent recognition that signaling by CD40 is initiated when the receptors are induced to cluster within the membrane of responding cells. This requirement for CD40 clustering explains the stimulatory effects of certain anti-CD40 antibodies and the activity of many-trimer, but not one-trimer, forms of CD40 ligand (CD40L, CD154). The second topic is the use of these CD40 activators to expand B cells ("CD40-B cells"). As antigen-presenting cells (APCs), CD40-B cells are as effective as dendritic cells, with the important difference that CD40 B cells can be induced to proliferate in vitro, whereas DCs proliferate poorly if at all. As a result, the use of CD40-B cells as antigen-presenting cells (APCs) promises to streamline the generation of anti-tumor CD8(+) T cells for the adoptive cell therapy (ACT) of cancer.
CD40 刺激在癌症患者的早期临床试验中产生了令人印象深刻的结果。通过更好地了解 CD40 受体如何被激活以及随后的 CD40 刺激免疫细胞的功能，将促进进一步的进展。这篇综述集中讨论了这个主题的两个方面。首先是最近认识到，当受体在反应细胞的膜内诱导聚集时，CD40 的信号转导就开始了。这种对 CD40 聚集的要求解释了某些抗 CD40 抗体的刺激作用以及许多三聚体而不是单三聚体形式的 CD40 配体（CD40L，CD154）的活性。第二个主题是使用这些 CD40 激活剂来扩增 B 细胞（“CD40-B 细胞”）。作为抗原呈递细胞（APCs），CD40-B 细胞与树突状细胞一样有效，重要的区别是 CD40-B 细胞可以在体外诱导增殖，而树突状细胞增殖不良甚至不增殖。因此，使用 CD40-B 细胞作为抗原呈递细胞（APCs）有望简化用于癌症过继细胞治疗（ACT）的抗肿瘤 CD8（+）T 细胞的产生。
