Open Access

ARTICLE

Oncolytic adenovirus H101 enhances the anti-tumor effects of PD-1 blockade via CD47 downregulation in tumor cells

CHENXIAO QIAO¹, YIPENG XU², YEDIE HE², ZHIJIAN CAI^1,*, HUA WANG^2,*

1 Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, 310058, China
2 Department of Urology, Zhejiang Cancer Hospital, Hangzhou, 310022, China

* Corresponding Authors: ZHIJIAN CAI. Email: ; HUA WANG. Email:

Oncology Research 2025, 33(5), 1161-1172. https://doi.org/10.32604/or.2024.055746

Received 06 July 2024; Accepted 25 October 2024; Issue published 18 April 2025

Abstract

Objective: 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. Methods: Anti-tumor efficacy of intratumoral injection of H101 or/and intraperitoneal injection of Camrelizumab were evaluated in an immune system humanized NOD Prkdc^scid Il2rg^-/- 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. Results: 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. Conclusion: The combination of H101 with PD-1 blockade exhibits potential as a novel strategy for the treatment of cancer.

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