A lentiviral vector allowing physiologically-regulated membrane-anchored and secreted antibody expression depending on B cell maturation status

Fusil F, Calattini S, Amirache F, Mancip J, Costa C, Robbins JB, Douam F, Lavillette D, Law M, Defrance T, Verhoeyen E, Cosset FL

Mol. Ther. 2015 Aug;

Abstract

PMID: 26281898

The development of lentiviral vectors for expression of a specific antibody can be achieved through the transduction of mature B cells. This approach would provide a versatile tool for active immunotherapy strategies for infectious diseases or cancer, as well as for protein engineering. Here, we created a lentiviral expression system mimicking the natural production of these two distinct immunoglobulin isoforms. We designed a lentiviral vector (FAM2-LV) expressing an anti-HCV-E2 surface glycoprotein antibody (AR3A) as a membrane-anchored Ig form or a soluble Ig form, depending on the B cell maturation status. FAM2-LV induced high-level and functional membrane expression of the transgenic antibody in a non-secretory B cell line. In contrast, a plasma cell (PC) line transduced with FAM2-LV preferentially produced the secreted transgenic antibody. Similar results were obtained with primary B cells transduced ex vivo. Most importantly, FAM2-LV transduced primary B cells efficiently differentiated into PCs, which secreted the neutralizing anti-HCV E2 antibody upon adoptive transfer into immunodeficient NSG (NOD/SCIDγc(-/-)) recipient miceAltogether, these results demonstrate that the conditional FAM2-LV allows preferential expression of the membrane-anchored form of an anti-viral neutralizing antibody in B cells and permits secretion of a soluble antibody following B cell maturation into PCs in vivo.Molecular Therapy (2015); doi:10.1038/mt.2015.148.