@Article{or.2024.055746,
AUTHOR = {CHENXIAO QIAO, YIPENG XU, YEDIE HE, ZHIJIAN CAI, HUA WANG},
TITLE = {Oncolytic adenovirus H101 enhances the anti-tumor effects of PD-1 blockade via CD47 downregulation in tumor cells},
JOURNAL = {Oncology Research},
VOLUME = {33},
YEAR = {2025},
NUMBER = {5},
PAGES = {1161--1172},
URL = {http://www.techscience.com/or/v33n5/60614},
ISSN = {1555-3906},
ABSTRACT = { <b>Objective:</b> 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. <b>Methods:</b> Anti-tumor efficacy of intratumoral injection of H101 or/and intraperitoneal injection of Camrelizumab were evaluated in an immune system humanized NOD <i>Prkdc</i><sup><i>scid</i></sup> <i>Il2rg</i><sup><i>-/-</i></sup> 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. <b>Results:</b> 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<sup>+</sup> T cells. <b>Conclusion:</b> The combination of H101 with PD-1 blockade exhibits potential as a novel strategy for the treatment of cancer.},
DOI = {10.32604/or.2024.055746}
}