The engineered agonistic anti-CD40 antibody potentiates the antitumor effects of β-glucan by resetting TAMs

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
Wanpeng Cheng , Ziyi Huang , Yongzhe Hao , Hui Hua , Bo Zhang , Xiangyang Li , Fengqing Fu , Jing Yang , Kuiyang Zheng , Xueguang Zhang , Chunjian Qi
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Abstract

Anti-CD40 antibodies (Abs) have been shown to induce antitumor T-cell responses. We reported that the engineered agonistic anti-CD40 Ab (5C11, IgG4 isotype) recognized human CD40 antigen expressed on a human B lymphoblastoid cell line as well as on splenic cells isolated from humanized CD40 mice. Of note, a single high dosage of 5C11 was able to prohibit tumor growth in parallel with an increase in the population of infiltrated CD8+ T cells. Furthermore, the antitumor effects of 5C11 were enhanced in the presence of β-glucan along with an increase in the population of infiltrated CD8+ T cells. In addition, the numbers of CD86+ TAMs and neutrophils were elevated in the combination of 5C11 and β-glucan compared with either 5C11 or β-glucan alone. Furthermore, the abundance of Faecalibaculum, one of the probiotics critical for tumor suppression, was obviously increased in the combination of 5C11 and β-glucan-treated mice. These data reveal a novel mechanism of tumor suppression upon the combination treatment of 5C11 and β-glucan and propose that the combination treatment of agonistic anti-human CD40 antibody 5C11 and β-glucan could be a promising therapeutic strategy for cancer patients.

经改造的激动型抗 CD40 抗体可通过重置 TAMs 增强β-葡聚糖的抗肿瘤作用。
抗 CD40 抗体(Abs)已被证明可诱导抗肿瘤 T 细胞反应。我们报告说,工程化的激动型抗 CD40 抗体(5C11,IgG4 同种型)能识别在人 B 淋巴母细胞系以及从人源化 CD40 小鼠分离的脾细胞上表达的人 CD40 抗原。值得注意的是,在增加浸润的 CD8+ T 细胞数量的同时,单次高剂量的 5C11 能够抑制肿瘤生长。此外,在β-葡聚糖存在的情况下,5C11的抗肿瘤作用会增强,同时浸润的CD8+ T细胞数量也会增加。此外,与单独使用 5C11 或 β-葡聚糖相比,联合使用 5C11 和 β-葡聚糖时 CD86+ TAMs 和中性粒细胞的数量增加。此外,在 5C11 和 β-葡聚糖联合治疗的小鼠中,对抑制肿瘤至关重要的益生菌之一 Faecalibaculum 的丰度明显增加。这些数据揭示了 5C11 和 β-葡聚糖联合治疗抑制肿瘤的新机制,并提出了激动剂抗人 CD40 抗体 5C11 和 β-葡聚糖联合治疗可能是癌症患者的一种有前途的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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