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Targeting lentiviral vectors to antigen-specific immunoglobulins

Ziegler, Leslie and Yang, Lili and Joo, Kye il and Yang, Haiguang and Baltimore, David and Wang, Pin (2008) Targeting lentiviral vectors to antigen-specific immunoglobulins. Human Gene Therapy, 19 (9). pp. 861-872. ISSN 1043-0342. PMCID PMC2599792.

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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 rnethod to target lentivectors to monospecific immunoglobulin-expressing cells in vitro and hi 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 (αCD20), 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 αCD20. 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.

Item Type:Article
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URLURL TypeDescription CentralArticle
Baltimore, David0000-0001-8723-8190
Additional Information:© Mary Ann Liebert, Inc. Received for publication November 9, 2007; accepted after revision June 29, 2008. Published online: August 14, 2008. The authors are grateful to Chi-Lin Lee and Sungjin Park for help in the preparation of figures, and Dinesh Rao and April Tai for critical reading of the manuscript. This work was supported by a grant from the National Institutes of Health (R01AI068978).
Funding AgencyGrant Number
Subject Keywords:B-cell lymphoma; chronic lymphocytic-leukemia; gene-therapy; autoimmune-disease; sindbis virus; in-vivo; low Ph; expression; antibodies; transduction
Issue or Number:9
PubMed Central ID:PMC2599792
Record Number:CaltechAUTHORS:ZIEhgt08
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:13358
Deposited By: Tony Diaz
Deposited On:23 Apr 2009 18:27
Last Modified:16 Apr 2020 22:45

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