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;
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.