Qiao Chenxiao, Xu Yipeng, He Yedie, Cai Zhijian, Wang Hua
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Department of Urology, Zhejiang Cancer Hospital, Hangzhou, 310022, China.
Oncol Res. 2025 Apr 18;33(5):1161-1172. doi: 10.32604/or.2024.055746. eCollection 2025.
To investigate the anti-tumor effects of an E1B55KD-deleted oncolytic adenovirus, H101, in combination with a humanized anti-PD-1 (Programmed cell death protein 1) monoclonal antibody, Camrelizumab.
Anti-tumor efficacy of intratumoral injection of H101 or/and intraperitoneal injection of Camrelizumab were evaluated in an immune system humanized NOD mice subcutaneous (S.C.) tumor model, established with human glioblastoma of unknown origin cell line U87-MG, and human bladder cancer cell line T24 and YTS-1. The mechanism by which H101 induced anti-tumor immunity were also investigated.
Combining H101 with Camrelizumab demonstrated more potent anti-tumor effects than monotherapy in mouse S.C. tumor model. Increased tumor-infiltrating T cells were observed in the combined treatment group. H101 infection decreased the expression of CD47 in cancer cells, thereby promoting macrophages to phagocytose cancer cells. Following the H101-mediated activation of macrophages, increased levels of cytokines, including TNF, IL-12 and IFN-γ were observed. Moreover, when induced THP-1 cells were co-cultured with H101-treated cancer cells, expression of IFN-γ was increased in T cells. Elimination of IL-12 using an anti-IL-12 antibody abolished IFN-γ production from T cells. In addition, infection with H101 increased PD-L1 expression in YTS-1 cells. These results suggested that H101 may act synergistically to enhance the therapeutic efficacy of PD-1 blockade in cancer via suppressing CD47 signaling, which may promote macrophages to phagocytose tumor cells and activate CD8 T cells.
The combination of H101 with PD-1 blockade exhibits potential as a novel strategy for the treatment of cancer.
研究缺失E1B55KD的溶瘤腺病毒H101与人源化抗程序性死亡蛋白1（PD-1）单克隆抗体卡瑞利珠单抗联合使用的抗肿瘤作用。
在用人源化免疫系统NOD小鼠建立的皮下（S.C.）肿瘤模型中，评估瘤内注射H101或/和腹腔注射卡瑞利珠单抗的抗肿瘤疗效，该模型使用来源不明的人胶质母细胞瘤细胞系U87-MG、人膀胱癌细胞系T24和YTS-1构建。同时研究H101诱导抗肿瘤免疫的机制。
在小鼠S.C.肿瘤模型中，H101与卡瑞利珠单抗联合使用显示出比单一疗法更强的抗肿瘤作用。联合治疗组中肿瘤浸润性T细胞增加。H101感染降低癌细胞中CD47的表达，从而促进巨噬细胞吞噬癌细胞。在H101介导的巨噬细胞激活后，观察到包括肿瘤坏死因子（TNF）、白细胞介素-12（IL-12）和干扰素-γ（IFN-γ）在内的细胞因子水平升高。此外，当诱导的THP-1细胞与H101处理的癌细胞共培养时，T细胞中IFN-γ的表达增加。使用抗IL-12抗体消除IL-12可消除T细胞产生的IFN-γ。此外，H101感染增加YTS-1细胞中PD-L1的表达。这些结果表明，H101可能通过抑制CD47信号协同增强PD-1阻断在癌症治疗中的疗效，这可能促进巨噬细胞吞噬肿瘤细胞并激活CD8 T细胞。
H101与PD-1阻断联合使用作为一种新型癌症治疗策略具有潜力。
