دورية أكاديمية
Evaluation of anti-vector immune responses to adenovirus-mediated lung gene therapy and modulation by αCD20
العنوان: | Evaluation of anti-vector immune responses to adenovirus-mediated lung gene therapy and modulation by αCD20 |
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المؤلفون: | Robert D.E. Clark, Felix Rabito, Ferris T. Munyonho, T. Parks Remcho, Jay K. Kolls |
المصدر: | Molecular Therapy: Methods & Clinical Development, Vol 32, Iss 3, Pp 101286- (2024) |
بيانات النشر: | Elsevier, 2024. |
سنة النشر: | 2024 |
المجموعة: | LCC:Genetics LCC:Cytology |
مصطلحات موضوعية: | cystic fibrosis, inhaled gene therapy, viral vectors, anti-CD20, host immune response, adenovirus, Genetics, QH426-470, Cytology, QH573-671 |
الوصف: | 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. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2329-0501 |
Relation: | http://www.sciencedirect.com/science/article/pii/S2329050124001025; https://doaj.org/toc/2329-0501 |
DOI: | 10.1016/j.omtm.2024.101286 |
URL الوصول: | https://doaj.org/article/472d5f630d7b4844bbaea67e9bc44cca |
رقم الأكسشن: | edsdoj.472d5f630d7b4844bbaea67e9bc44cca |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 23290501 |
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DOI: | 10.1016/j.omtm.2024.101286 |