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Velazquez VM, Meadows AS, Pineda RJ, et al. Effective Depletion of Pre-existing Anti-AAV Antibodies Requires Broad Immune Targeting. Mol Ther Methods Clin Dev. 2017;4:159-168doi: 10.1016/j.omtm.2017.01.003.
Velazquez, V. M., Meadows, A. S., Pineda, R. J., Camboni, M., McCarty, D. M., & Fu, H. (2017). Effective Depletion of Pre-existing Anti-AAV Antibodies Requires Broad Immune Targeting. Molecular therapy. Methods & clinical development, 4159-168. https://doi.org/10.1016/j.omtm.2017.01.003
Velazquez, Victoria M, et al. "Effective Depletion of Pre-existing Anti-AAV Antibodies Requires Broad Immune Targeting." Molecular therapy. Methods & clinical development vol. 4 (2017): 159-168. doi: https://doi.org/10.1016/j.omtm.2017.01.003
Velazquez VM, Meadows AS, Pineda RJ, Camboni M, McCarty DM, Fu H. Effective Depletion of Pre-existing Anti-AAV Antibodies Requires Broad Immune Targeting. Mol Ther Methods Clin Dev. 2017 Jan 25;4:159-168. doi: 10.1016/j.omtm.2017.01.003. eCollection 2017 Mar 17. PMID: 28345001; PMCID: PMC5363314.
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Mol Ther Methods Clin Dev. 2017 Jan 25;4:159-168. doi: 10.1016/j.omtm.2017.01.003. eCollection 2017 Mar 17.

Effective Depletion of Pre-existing Anti-AAV Antibodies Requires Broad Immune Targeting.

Molecular therapy. Methods & clinical development

Victoria M Velazquez, Aaron S Meadows, Ricardo J Pineda, Marybeth Camboni, Douglas M McCarty, Haiyan Fu

Affiliations

  1. Center for Vaccine and Immunology, Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
  2. Center for Gene Therapy, Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
  3. Center for Gene Therapy, Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA; Department of Pediatrics, School of Medicine, The Ohio State University, Columbus, OH 43210, USA.

PMID: 28345001 PMCID: PMC5363314 DOI: 10.1016/j.omtm.2017.01.003

Abstract

Pre-existing antibodies (Abs) to AAV pose a critical challenge for the translation of gene therapies. No effective approach is available to overcome pre-existing Abs. Given the complexity of Ab production, overcoming pre-existing Abs will require broad immune targeting. We generated a mouse model of pre-existing AAV9 Abs to test multiple immunosuppressants, including bortezomib, rapamycin, and prednisolone, individually or in combination. We identified an effective approach combining rapamycin and prednisolone, reducing serum AAV9 Abs by 70%-80% at 4 weeks and 85%-93% at 8 weeks of treatment. The rapamycin plus prednisolone treatment resulted in significant decreases in the frequency of B cells, plasma cells, and IgG-secreting and AAV9-specific Ab-producing plasma cells in bone marrow. The rapamycin plus prednisolone treatment also significantly reduced frequencies of IgD

Keywords: AAV; gene therapy; pre-existing antibody

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