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.
摘要：
已显示抗CD40抗体(Ab)诱导抗肿瘤T细胞应答。我们报道了工程化的激动性抗CD40Ab（5C11，IgG4同种型）识别在人B淋巴母细胞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，单次高剂量5C11能够抑制肿瘤生长,同时增加浸润CD8+T细胞的数量.此外，在存在β-葡聚糖的情况下,5C11的抗肿瘤作用随着浸润CD8+T细胞数量的增加而增强.此外,与单独使用5C11或β-葡聚糖相比，5C11和β-葡聚糖的组合中CD86TAM和中性粒细胞的数量升高。此外，丰富的Faecalibaculum，对肿瘤抑制至关重要的益生菌之一，在5C11和β-葡聚糖处理的小鼠的组合中明显增加。这些数据揭示了在5C11和β-葡聚糖的组合治疗后肿瘤抑制的新机制,并且提出激动性抗人CD40抗体5C11和β-葡聚糖的组合治疗可能是癌症患者的有希望的治疗策略。
