Inducing expression of ICOS-L by oncolytic adenovirus to enhance tumor-specific bi-specific antibody efficacy
© 2024. The Author(s)..
BACKGROUND: Intratumoral injection of oncolytic viruses (OVs) shows promise in immunotherapy: ONCOS-102, a genetically engineered OV that encodes Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) demonstrated efficacy in early clinical trials, enhancing T cell infiltration in tumors. This suggests OVs may boost various forms of immunotherapy, including tumor-specific bi-specific antibodies (BsAbs).
METHODS: Our study investigated in vitro, how ONCOS-204, a variant of ONCOS-virus expressing the ligand of inducible T-cell co-stimulator (ICOSL), modulates the process of T cell activation induced by a BsAb. ONCOS-102 was used for comparison. Phenotypic and functional changes induced by combination of different OVs, and BsAb in T cell subsets were assessed by flow cytometry, viability, and proliferation assays.
RESULTS: Degranulation and IFNγ and TNF production of T cells, especially CD4 + T cells was the most increased upon target cell exposure to ONCOS-204. Unexpectedly, ONCOS-204 profoundly affected CD8 + T cell proliferation and function through ICOS-L/ICOS interaction. The effect solely depended on cell surface expression of ICOS-L as soluble ICOSL did not induce notable T cell activity.
CONCLUSIONS: Together, our data suggests that oncolytic adenoviruses encoding ICOSL may enhance functional activity of tumor-specific BsAbs thereby opening a novel avenue for clinical development in immunotherapeutics.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2024 |
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Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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Enthalten in: |
Journal of translational medicine - 22(2024), 1 vom: 07. März, Seite 250 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Saffarzadeh, Neshat [VerfasserIn] |
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Links: |
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Themen: |
Antibodies |
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Anmerkungen: |
Date Completed 11.03.2024 Date Revised 11.03.2024 published: Electronic Citation Status MEDLINE |
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doi: |
10.1186/s12967-024-05049-2 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM36944132X |
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520 | |a BACKGROUND: Intratumoral injection of oncolytic viruses (OVs) shows promise in immunotherapy: ONCOS-102, a genetically engineered OV that encodes Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) demonstrated efficacy in early clinical trials, enhancing T cell infiltration in tumors. This suggests OVs may boost various forms of immunotherapy, including tumor-specific bi-specific antibodies (BsAbs) | ||
520 | |a METHODS: Our study investigated in vitro, how ONCOS-204, a variant of ONCOS-virus expressing the ligand of inducible T-cell co-stimulator (ICOSL), modulates the process of T cell activation induced by a BsAb. ONCOS-102 was used for comparison. Phenotypic and functional changes induced by combination of different OVs, and BsAb in T cell subsets were assessed by flow cytometry, viability, and proliferation assays | ||
520 | |a RESULTS: Degranulation and IFNγ and TNF production of T cells, especially CD4 + T cells was the most increased upon target cell exposure to ONCOS-204. Unexpectedly, ONCOS-204 profoundly affected CD8 + T cell proliferation and function through ICOS-L/ICOS interaction. The effect solely depended on cell surface expression of ICOS-L as soluble ICOSL did not induce notable T cell activity | ||
520 | |a CONCLUSIONS: Together, our data suggests that oncolytic adenoviruses encoding ICOSL may enhance functional activity of tumor-specific BsAbs thereby opening a novel avenue for clinical development in immunotherapeutics | ||
650 | 4 | |a Journal Article | |
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700 | 1 | |a Levitsky, Victor |e verfasserin |4 aut | |
700 | 1 | |a Poiret, Thomas |e verfasserin |4 aut | |
700 | 1 | |a Uhlin, Michael |e verfasserin |4 aut | |
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