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

IF 3.3 4区 医学 Q3 IMMUNOLOGY
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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引用次数: 0

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
Immunology letters
Immunology letters 医学-免疫学
CiteScore
7.60
自引率
0.00%
发文量
86
审稿时长
44 days
期刊介绍: Immunology Letters provides a vehicle for the speedy publication of experimental papers, (mini)Reviews and Letters to the Editor addressing all aspects of molecular and cellular immunology. The essential criteria for publication will be clarity, experimental soundness and novelty. Results contradictory to current accepted thinking or ideas divergent from actual dogmas will be considered for publication provided that they are based on solid experimental findings. Preference will be given to papers of immediate importance to other investigators, either by their experimental data, new ideas or new methodology. Scientific correspondence to the Editor-in-Chief related to the published papers may also be accepted provided that they are short and scientifically relevant to the papers mentioned, in order to provide a continuing forum for discussion.
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