Targeting Lentiviral Vectors to Antigen-Specific Immunoglobulins

Gene transfer into B cells by lentivectors can provide an alternative approach to managing B lymphocyte malignancies and autoreactive B cell-mediated autoimmune diseases.These pathogenic B cell populations can be distinguished by their surface expression of monospecific immunoglobulin.Development of a novel vector system to deliver genes to these specific B cells could improve the safety and efficacy of gene therapy.We have developed an efficient method to target lentivectors to monospecific immunoglobulin-expressing cells in vitro and in vivo.We were able to incorporate a model antigen CD20 and a fusogenic protein derived from the Sindbis virus as two distinct molecules into the lentiviral surface.This engineered vector could specifically bind to cells expressing surface immunoglobulin recognizing CD20 (␣CD20), resulting in efficient transduction of target cells in a cognate antigen-dependent manner in vitro, and in vivo in a xenografted tumor model.Tumor suppression was observed in vivo, using the engineered lentivector to deliver a suicide gene to a xenografted tumor expressing ␣CD20.These results show the feasibility of engineering lentivectors to target immunoglobulin-specific cells to deliver a therapeutic effect.Such targeting lentivectors also could potentially be used to genetically mark antigen-specific B cells in vivo to study their B cell biology.