Neospora caninum as delivery vehicle for anti-PD-L1 scFv-Fc: A novel approach for cancer immunotherapy
Neospora caninum, a potential anticancer agent able to reactivate the immune response within the tumor microenvironment (TME), has recently shown enhanced immunomodulatory properties in different tumor models when armed with the cytokine, Il-15. In the current area of combination immunotherapy strat...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Molecular Therapy: Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950329925000372 |
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| author | Clément Riviere Muna Aljieli Marie-Noëlle Mévélec Louis Lantier Fanny Boursin Laurie Lajoie Céline Ducournau Stéphanie Germon Nathalie Moiré Isabelle Dimier-Poisson Nicolas Aubrey Anne di Tommaso |
| author_facet | Clément Riviere Muna Aljieli Marie-Noëlle Mévélec Louis Lantier Fanny Boursin Laurie Lajoie Céline Ducournau Stéphanie Germon Nathalie Moiré Isabelle Dimier-Poisson Nicolas Aubrey Anne di Tommaso |
| author_sort | Clément Riviere |
| collection | DOAJ |
| description | Neospora caninum, a potential anticancer agent able to reactivate the immune response within the tumor microenvironment (TME), has recently shown enhanced immunomodulatory properties in different tumor models when armed with the cytokine, Il-15. In the current area of combination immunotherapy strategies designed to overcome treatment resistance, we engineered for the first time the protozoan Neospora caninum to vectorize and secrete a single-chain variable fragment fused to fragment crystallizable region (scFv-Fc) targeting human programmed cell death ligand 1 (PD-L1). Following validation of its secretion through the micronemes (protozoa secretory organelles), we demonstrated that the scFv-Fc could bind PD-L1 on mouse and human tumor cells, block the programmed cell death protein 1 (PD-1)/PD-L1 pathway leading to potentiate the T cell lymphocyte activity. Additionally, the scFv-Fc induced antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC). Those data demonstrate the feasibility of vectoring and secreting a functional antibody fragment by N. caninum, opening promising avenues for future research. |
| format | Article |
| id | doaj-art-c501c87df0df4304ac22dbbd81fc09b6 |
| institution | OA Journals |
| issn | 2950-3299 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncology |
| spelling | doaj-art-c501c87df0df4304ac22dbbd81fc09b62025-08-20T01:55:11ZengElsevierMolecular Therapy: Oncology2950-32992025-06-0133220096810.1016/j.omton.2025.200968Neospora caninum as delivery vehicle for anti-PD-L1 scFv-Fc: A novel approach for cancer immunotherapyClément Riviere0Muna Aljieli1Marie-Noëlle Mévélec2Louis Lantier3Fanny Boursin4Laurie Lajoie5Céline Ducournau6Stéphanie Germon7Nathalie Moiré8Isabelle Dimier-Poisson9Nicolas Aubrey10Anne di Tommaso11BioMAP, UMR ISP 1282 INRAe – Université de Tours, 37200 Tours, FranceBioMAP, UMR ISP 1282 INRAe – Université de Tours, 37200 Tours, France; Faculty of Pharmacy, University of Gezira, Wad Madani, SudanBioMAP, UMR ISP 1282 INRAe – Université de Tours, 37200 Tours, FranceBioMAP, UMR ISP 1282 INRAe – Université de Tours, 37200 Tours, FranceBioMAP, UMR ISP 1282 INRAe – Université de Tours, 37200 Tours, FranceBioMAP, UMR ISP 1282 INRAe – Université de Tours, 37200 Tours, FranceBioMAP, UMR ISP 1282 INRAe – Université de Tours, 37200 Tours, FranceBioMAP, UMR ISP 1282 INRAe – Université de Tours, 37200 Tours, FranceBioMAP, UMR ISP 1282 INRAe – Université de Tours, 37200 Tours, FranceBioMAP, UMR ISP 1282 INRAe – Université de Tours, 37200 Tours, FranceBioMAP, UMR ISP 1282 INRAe – Université de Tours, 37200 Tours, FranceBioMAP, UMR ISP 1282 INRAe – Université de Tours, 37200 Tours, France; Corresponding author: Anne di Tommaso, BioMAP, UMR ISP 1282 INRAe – Université de Tours, 37200 Tours, France.Neospora caninum, a potential anticancer agent able to reactivate the immune response within the tumor microenvironment (TME), has recently shown enhanced immunomodulatory properties in different tumor models when armed with the cytokine, Il-15. In the current area of combination immunotherapy strategies designed to overcome treatment resistance, we engineered for the first time the protozoan Neospora caninum to vectorize and secrete a single-chain variable fragment fused to fragment crystallizable region (scFv-Fc) targeting human programmed cell death ligand 1 (PD-L1). Following validation of its secretion through the micronemes (protozoa secretory organelles), we demonstrated that the scFv-Fc could bind PD-L1 on mouse and human tumor cells, block the programmed cell death protein 1 (PD-1)/PD-L1 pathway leading to potentiate the T cell lymphocyte activity. Additionally, the scFv-Fc induced antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC). Those data demonstrate the feasibility of vectoring and secreting a functional antibody fragment by N. caninum, opening promising avenues for future research.http://www.sciencedirect.com/science/article/pii/S2950329925000372MT: Regular IssueNeospora caninumantibody fragmentscFv-Fcsecretioncancer immunotherapy |
| spellingShingle | Clément Riviere Muna Aljieli Marie-Noëlle Mévélec Louis Lantier Fanny Boursin Laurie Lajoie Céline Ducournau Stéphanie Germon Nathalie Moiré Isabelle Dimier-Poisson Nicolas Aubrey Anne di Tommaso Neospora caninum as delivery vehicle for anti-PD-L1 scFv-Fc: A novel approach for cancer immunotherapy Molecular Therapy: Oncology MT: Regular Issue Neospora caninum antibody fragment scFv-Fc secretion cancer immunotherapy |
| title | Neospora caninum as delivery vehicle for anti-PD-L1 scFv-Fc: A novel approach for cancer immunotherapy |
| title_full | Neospora caninum as delivery vehicle for anti-PD-L1 scFv-Fc: A novel approach for cancer immunotherapy |
| title_fullStr | Neospora caninum as delivery vehicle for anti-PD-L1 scFv-Fc: A novel approach for cancer immunotherapy |
| title_full_unstemmed | Neospora caninum as delivery vehicle for anti-PD-L1 scFv-Fc: A novel approach for cancer immunotherapy |
| title_short | Neospora caninum as delivery vehicle for anti-PD-L1 scFv-Fc: A novel approach for cancer immunotherapy |
| title_sort | neospora caninum as delivery vehicle for anti pd l1 scfv fc a novel approach for cancer immunotherapy |
| topic | MT: Regular Issue Neospora caninum antibody fragment scFv-Fc secretion cancer immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2950329925000372 |
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