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Wang X, Herzog RW, Byrne BJ, et al. Immune Modulatory Cell Therapy for Hemophilia B Based on CD20-Targeted Lentiviral Gene Transfer to Primary B Cells. Mol Ther Methods Clin Dev. 2017;5:76-82doi: 10.1016/j.omtm.2017.03.005.
Wang, X., Herzog, R. W., Byrne, B. J., Kumar, S. R. P., Zhou, Q., Buchholz, C. J., & Biswas, M. (2017). Immune Modulatory Cell Therapy for Hemophilia B Based on CD20-Targeted Lentiviral Gene Transfer to Primary B Cells. Molecular therapy. Methods & clinical development, 576-82. https://doi.org/10.1016/j.omtm.2017.03.005
Wang, Xiaomei, et al. "Immune Modulatory Cell Therapy for Hemophilia B Based on CD20-Targeted Lentiviral Gene Transfer to Primary B Cells." Molecular therapy. Methods & clinical development vol. 5 (2017): 76-82. doi: https://doi.org/10.1016/j.omtm.2017.03.005
Wang X, Herzog RW, Byrne BJ, Kumar SRP, Zhou Q, Buchholz CJ, Biswas M. Immune Modulatory Cell Therapy for Hemophilia B Based on CD20-Targeted Lentiviral Gene Transfer to Primary B Cells. Mol Ther Methods Clin Dev. 2017 Mar 29;5:76-82. doi: 10.1016/j.omtm.2017.03.005. eCollection 2017 Jun 16. PMID: 28480307; PMCID: PMC5415320.
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Mol Ther Methods Clin Dev. 2017 Mar 29;5:76-82. doi: 10.1016/j.omtm.2017.03.005. eCollection 2017 Jun 16.

Immune Modulatory Cell Therapy for Hemophilia B Based on CD20-Targeted Lentiviral Gene Transfer to Primary B Cells.

Molecular therapy. Methods & clinical development

Xiaomei Wang, Roland W Herzog, Barry J Byrne, Sandeep R P Kumar, Qi Zhou, Christian J Buchholz, Moanaro Biswas

Affiliations

  1. Division of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA.
  2. Powell Gene Therapy Center, Department of Pediatrics, University of Florida, Gainesville, FL 32610, USA.
  3. Molecular Biotechnology and Gene Therapy, Paul-Ehrlich-Institut, 63225 Langen, Germany.

PMID: 28480307 PMCID: PMC5415320 DOI: 10.1016/j.omtm.2017.03.005

Abstract

Gene-modified B cells expressing immunoglobulin G (IgG) fusion proteins have been shown to induce tolerance in several autoimmune and other disease models. However, lack of a vector suitable for gene transfer to human B cells has been an obstacle for translation of this approach. To overcome this hurdle, we developed an IgG-human factor IX (hFIX) lentiviral fusion construct that was targeted to specifically transduce cells expressing human CD20 (hCD20). Receptor-specific retargeting by mutating envelope glycoproteins of measles virus (MV)-lentiviral vector (LV) and addition of a single-chain variable fragment specific for hCD20 resulted in gene delivery into primary human and transgenic hCD20 mouse B cells with high specificity. Notably, this protocol neither required nor induced activation of the B cells, as confirmed by minimal activation of inflammatory cytokines. Using this strategy, we were able to demonstrate induction of humoral tolerance, resulting in suppression of antibody formation against hFIX in a mouse model of hemophilia B (HB). In conclusion, transduction of receptor-specific retargeted LV into resting B cells is a promising method to develop B cell therapies for antigen-specific tolerance induction in human disease.

Keywords: CD20; SCFV; gene transfer; hemophilia B; lentivirus; measles virus; psuedotype

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