Abstract
The ability of B cells to function as tolerogenic antigen presenting cells (APCs) in vitro and in vivo, makes them ideal targets for gene therapy strategies focused on the induction and re-establishment of tolerance. Current therapy methods employ retroviral vectors for infection of B cells or bone marrow cells and subsequent expression of the target antigen. Moreover, the efficacy of peptide-IgG fusion constructs which take advantage of the tolerogenic properties of IgG has been demonstrated. In this review, we discuss gene therapy approaches mediated by B cells and bone marrow cells for tolerance acquisition in various mouse models for autoimmune disease, hemophilia and transplantation. The results indicate that gene therapy strategies successfully reduce the incidence of disease, or delay disease onset in multiple mouse models for autoimmune disease and hemophilia. Additionally, gene therapy has proven effective in a mouse transplantation model. While these studies show great promise, the mechanisms involved in tolerance, including the role of regulatory T cells, will need to be more clearly defined before the transition to a clinical setting can occur.
Keywords: tolerance, B cells, gene therapy, immunoglobulin fusions, retroviral vector, antigen presentation, autoimmunity, hemophilia, transplantation, bone marrow cells
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Title: B-Cell Based Gene Therapy for Inducing Tolerance
Volume: 6 Issue: 2
Author(s): Indira Carey, Yan Su, Yufei Jiang, Jonathan Skupsky and David W. Scott
Affiliation:
Keywords: tolerance, B cells, gene therapy, immunoglobulin fusions, retroviral vector, antigen presentation, autoimmunity, hemophilia, transplantation, bone marrow cells
Abstract: The ability of B cells to function as tolerogenic antigen presenting cells (APCs) in vitro and in vivo, makes them ideal targets for gene therapy strategies focused on the induction and re-establishment of tolerance. Current therapy methods employ retroviral vectors for infection of B cells or bone marrow cells and subsequent expression of the target antigen. Moreover, the efficacy of peptide-IgG fusion constructs which take advantage of the tolerogenic properties of IgG has been demonstrated. In this review, we discuss gene therapy approaches mediated by B cells and bone marrow cells for tolerance acquisition in various mouse models for autoimmune disease, hemophilia and transplantation. The results indicate that gene therapy strategies successfully reduce the incidence of disease, or delay disease onset in multiple mouse models for autoimmune disease and hemophilia. Additionally, gene therapy has proven effective in a mouse transplantation model. While these studies show great promise, the mechanisms involved in tolerance, including the role of regulatory T cells, will need to be more clearly defined before the transition to a clinical setting can occur.
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Cite this article as:
Carey Indira, Su Yan, Jiang Yufei, Skupsky Jonathan and Scott W. David, B-Cell Based Gene Therapy for Inducing Tolerance, Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 2007; 6 (2) . https://dx.doi.org/10.2174/187152307780598072
DOI https://dx.doi.org/10.2174/187152307780598072 |
Print ISSN 1871-5230 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-614X |
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