ArticleJournal for immunotherapy of cancer2024
Engineered oncolytic virus expressing B7H3-targeting BiTE enhances antitumor T-cell immune response.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Next-generation oncolytic virotherapy for lung cancer: bridging innovative vector engineering with clinical immunotherapy.Translational lung cancer research · 2026Review
- Integrating oncolytic adenoviruses into combination cancer therapy: Mechanisms, advances and clinical outlook.Clinical and translational medicine · 2026Review
- Oncolytic adenoviruses encoding bispecific T cell engagers or a novel trispecific T cell engager for dual-targeting of c-MET and EGFR.Molecular therapy. Oncology · 2026Article
- Engineering antibody-armed oncolytic viruses: design strategies, synergistic mechanisms, and clinical translation.Frontiers in immunology · 2026Review
- Review
- Immuno-oncology recapitulates ontogeny: Modern cell and gene therapy for cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Engaging T cells for cleanup.Frontiers in immunology · 2025Review
- Bispecific immunotherapy based on antibodies, T-cell receptors, and aptamers: mechanisms of action, adverse effects, and future perspectives.Frontiers in immunology · 2025Review
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Authors and funding
6 authors.
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Abstract
backgroundBispecific T-cell engagers (BiTEs) are recombinant bispecific proteins designed to stimulate polyclonal T-cell immunity. In recent years, B7H3, a pan-cancer antigen, has been considered a promising target for future immunotherapy. However, the B7H3-targeting BiTE faces the challenge of systemic toxicity. Oncolytic viruses (OVs) represent a new class of cancer immunotherapeutics and serve as an appropriate platform for locoregional delivery of therapeutic genes. In this study, we designed an oncolytic adenovirus (OAd) encoding BiTE targeting human B7H3. We hypothesized that OVs encoding B7H3 BiTE deliver this molecule persistently to the tumor site while mediating polyclonal T-cell activation and redirecting it to tumor cells.
methodsB7H3-targeting BiTE was constructed by linking a single-chain variable fragment (scFv) that recognizes human B7H3 to an scFv that recognizes human CD3. B7H3 BiTE was inserted into OAd to construct OAd-B7H3-BiTE. The function of the OV-delivered B7H3 BiTE was detected via co-culturing B7H3
resultsB7H3 is highly expressed in a high proportion of human malignancies. OV-delivered BiTEs bind to T cells and target cells. We observed a series of phenomena reflecting T-cell activation induced by OAd-B7H3-BiTE, including cell clustering, cell size, activation markers, cytokine secretion, and proliferation. Furthermore, T-cell activation was mirrored by the corresponding cytotoxicity against B7H3
conclusionsUsing an OV for the local expression of B7H3 BiTE maximizes the local concentration of BiTE while reducing systemic exposure. OV also provides a relatively "hot" T-cell immune environment for the function of BiTE. Because of its capacity to activate polyclonal T cells, BiTE has the potential to redirect virus-specific T cells to tumors. Our study provides new opportunities for the exploitation of B7H3-BiTE-armed OVs as therapeutic agents for the treatment of B7H3-positive malignancies.
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