Wennhold Kerstin, Shimabukuro-Vornhagen Alexander, von Bergwelt-Baildon Michael
Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
Department I for Internal Medicine, University Hospital Cologne, Cologne, Germany.
Transfus Med Hemother. 2019 Feb;46(1):36-46. doi: 10.1159/000496166. Epub 2019 Feb 4.
B cells are not only producers of antibodies, but also contribute to immune regulation or act as potent antigen-presenting cells. The potential of B cells for cellular therapy is still largely underestimated, despite their multiple diverse effector functions. The CD40L/CD40 signaling pathway is the most potent activator of antigen presentation capacity in B lymphocytes. CD40-activated B cells are potent antigen-presenting cells that induce specific T-cell responses in vitro and in vivo. In preclinical cancer models in mice and dogs, CD40-activated B cell-based cancer immunotherapy was able to induce effective antitumor immunity. So far, there have been only few early-stage clinical studies involving B cell-based cancer vaccines. These trials indicate that B cell-based immunotherapy is generally safe and associated with little toxicity. Furthermore, these studies suggest that B-cell immunotherapy can elicit antitumor T-cell responses. Alongside the recent advances in cellular therapies in general, major obstacles for generation of good manufacturing practice-manufactured B-cell immunotherapies have been overcome. Thus, a first clinical trial involving CD40-activated B cells might be in reach.
B细胞不仅是抗体的产生者,还对免疫调节有贡献或作为强大的抗原呈递细胞。尽管B细胞具有多种不同的效应功能,但其在细胞治疗方面的潜力仍在很大程度上被低估。CD40L/CD40信号通路是B淋巴细胞中抗原呈递能力最有效的激活剂。CD40激活的B细胞是强大的抗原呈递细胞,可在体外和体内诱导特异性T细胞反应。在小鼠和犬的临床前癌症模型中,基于CD40激活的B细胞的癌症免疫疗法能够诱导有效的抗肿瘤免疫。到目前为止,仅有少数涉及基于B细胞的癌症疫苗的早期临床研究。这些试验表明,基于B细胞的免疫疗法总体上是安全的,且毒性很小。此外,这些研究表明,B细胞免疫疗法可引发抗肿瘤T细胞反应。随着细胞治疗领域总体上的最新进展,生产符合药品生产质量管理规范的B细胞免疫疗法的主要障碍已被克服。因此,首个涉及CD40激活的B细胞的临床试验可能即将开展。