BMFPs, a versatile therapeutic tool for redirecting a preexisting Epstein-Barr virus antibody response toward defined target cells.

Autor:	Gamain B; Université de Paris, Biologie Intégrée du Globule Rouge, UMR_S1134, INSERM, F-75015 Paris, France., Brousse C; Université de Paris, Biologie Intégrée du Globule Rouge, UMR_S1134, INSERM, F-75015 Paris, France., Rainey NE; Université de Paris, Biologie Intégrée du Globule Rouge, UMR_S1134, INSERM, F-75015 Paris, France., Diallo BK; Laboratory 'Immune Microenvironment and Immunotherapy', INSERM U.1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Faculté de Médecine, Sorbonne Université, 91 boulevard de l'Hôpital, 75013 Paris, France., Paquereau CE; Université de Paris, Biologie Intégrée du Globule Rouge, UMR_S1134, INSERM, F-75015 Paris, France., Desrames A; Université de Paris, Biologie Intégrée du Globule Rouge, UMR_S1134, INSERM, F-75015 Paris, France., Ceputyte J; Université de Paris, Biologie Intégrée du Globule Rouge, UMR_S1134, INSERM, F-75015 Paris, France., Semblat JP; Université de Paris, Biologie Intégrée du Globule Rouge, UMR_S1134, INSERM, F-75015 Paris, France., Bertrand O; Université de Paris, Biologie Intégrée du Globule Rouge, UMR_S1134, INSERM, F-75015 Paris, France., Gangnard S; Université de Paris, Biologie Intégrée du Globule Rouge, UMR_S1134, INSERM, F-75015 Paris, France., Teillaud JL; Laboratory 'Immune Microenvironment and Immunotherapy', INSERM U.1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Faculté de Médecine, Sorbonne Université, 91 boulevard de l'Hôpital, 75013 Paris, France., Chêne A; Université de Paris, Biologie Intégrée du Globule Rouge, UMR_S1134, INSERM, F-75015 Paris, France.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2022 Feb 11; Vol. 8 (6), pp. eabl4363. Date of Electronic Publication: 2022 Feb 11.
DOI:	10.1126/sciadv.abl4363
Abstrakt:	Industrial production of therapeutic monoclonal antibodies is mostly performed in eukaryotic-based systems, allowing posttranslational modifications mandatory for their functional activity. The resulting elevated product cost limits therapy access to some patients. To address this limitation, we conceptualized a novel immunotherapeutic approach to redirect a preexisting polyclonal antibody response against Epstein-Barr virus (EBV) toward defined target cells. We engineered and expressed in bacteria bimodular fusion proteins (BMFPs) comprising an Fc-deficient binding moiety targeting an antigen expressed at the surface of a target cell, fused to the EBV-P18 antigen, which recruits circulating endogenous anti-P18 IgG in EBV + individuals. Opsonization of BMFP-coated targets efficiently triggered antibody-mediated clearing effector mechanisms. When assessed in a P18-primed mouse tumor model, therapy performed with an anti-huCD20 BMFP significantly led to increased survival and total cancer remission in some animals. These results indicate that BMFPs could represent potent and useful therapeutic molecules to treat a number of diseases.
Databáze:	MEDLINE
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