Neospora caninum as delivery vehicle for anti-PD-L1 scFv-Fc: A novel approach for cancer immunotherapy
2025
Rivière, Clément | Aljieli, Muna | Mévélec, Marie-Noëlle | Lantier, Louis | Boursin, Fanny | Lajoie, Laurie | Ducournau, Céline | Germon, Stéphanie | Moiré, Nathalie | Dimier-Poisson, Isabelle | Aubrey, Nicolas | Di Tommaso, Anne | Infectiologie et Santé Publique (ISP) ; Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | University of Gezira [Wad Madani, Sudan] [University of al-Jazirah] = جامعة الجزيرة (U. of G.) | This work was supported by the Region Centre-Val de Loire, the Laboratoire d'Excellence (LabEx) "MabImprove" (to C.R.) , and the University of Tours, France. | ANR-10-LABX-0053,MAbImprove,Optimization of therapeutic monoclonal antibodies development Better antibodies, better developed AND better used(2010)
International audience
اظهر المزيد [+] اقل [-]إنجليزي. 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.
اظهر المزيد [+] اقل [-]الكلمات المفتاحية الخاصة بالمكنز الزراعي (أجروفوك)
المعلومات البيبليوغرافية
تم تزويد هذا السجل من قبل Institut national de la recherche agronomique