| Autor: |
Robert D.E. Clark, Felix Rabito, Ferris T. Munyonho, T. Parks Remcho, Jay K. Kolls |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Methods & Clinical Development, Vol 32, Iss 3, Pp 101286- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2329-0501 |
| DOI: |
10.1016/j.omtm.2024.101286 |
| Popis: |
Although the last decade has seen tremendous progress in drugs that treat cystic fibrosis (CF) due to mutations that lead to protein misfolding, there are approximately 8%–10% of subjects with mutations that result in no significant CFTR protein expression demonstrating the need for gene editing or gene replacement with inhaled mRNA or vector-based approaches. A limitation for vector-based approaches is the formation of neutralizing humoral responses. Given that αCD20 has been used to manage post-transplant lymphoproliferative disease in CF subjects with lung transplants, we studied the ability of αCD20 to module both T and B cell responses in the lung to one of the most immunogenic vectors, E1-deleted adenovirus serotype 5. We found that αCD20 significantly blocked luminal antibody responses and efficiently permitted re-dosing. αCD20 had more limited impact on the T cell compartment, but reduced tissue resident memory T cell responses in bronchoalveolar lavage fluid. Taken together, these pre-clinical studies suggest that αCD20 could be re-purposed for lung gene therapy protocols to permit re-dosing. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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