Details

Autor(en) / Beteiligte

• Gamain, Benoît
• Brousse, Carine
• Rainey, Nathan E
• Diallo, Béré K
• Paquereau, Clara-Eva
• Desrames, Alexandra
• Ceputyte, Jolita
• Semblat, Jean-Philippe
• Bertrand, Olivier
• Gangnard, Stéphane
• Teillaud, Jean-Luc
• Chêne, Arnaud

Titel

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

Ist Teil von

• Science advances, 2022-02, Vol.8 (6), p.eabl4363-eabl4363

Ort / Verlag

United States: American Association for the Advancement of Science (AAAS)

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.