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Article Dans Une Revue Science Advances Année : 2022

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

Résumé

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.
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Dates et versions

hal-03573011 , version 1 (14-02-2022)

Identifiants

Citer

Benoît Gamain, Carine Brousse, Nathan E Rainey, Béré K Diallo, Clara-Eva Paquereau, et al.. BMFPs, a versatile therapeutic tool for redirecting a preexisting Epstein-Barr virus antibody response toward defined target cells. Science Advances , 2022, 8 (6), pp.eabl4363. ⟨10.1126/sciadv.abl4363⟩. ⟨hal-03573011⟩
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