دورية أكاديمية
Tumor antigen-loaded AAV vaccine drives protective immunity in a melanoma animal model
| العنوان: | Tumor antigen-loaded AAV vaccine drives protective immunity in a melanoma animal model |
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| المؤلفون: | Karina Krotova, Hisae Kuoch (Yoshitomi), Colin Caine, George Aslanidi |
| المصدر: | Molecular Therapy: Methods & Clinical Development, Vol 28, Iss , Pp 301-311 (2023) |
| بيانات النشر: | Elsevier, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Genetics LCC:Cytology |
| مصطلحات موضوعية: | adeno-associated virus, cancer vaccine, self-antigen, antigen-specific T cell, protective immune response, syngeneic animal model, Genetics, QH426-470, Cytology, QH573-671 |
| الوصف: | We previously described therapeutic opportunities provided by capsid- and expression cassette-optimized adeno-associated virus serotype 6 (AAV6) vectors to suppress tumor growth in both solid and metastatic mouse models by using artificial ovalbumin (OVA) immunogen. In the current study, we further elucidated the mechanism of function of a novel AAV-based vaccine loaded with the melanoma tumor-associated antigens premelanosome protein gp100, tyrosinase (Tyr), tyrosinase-related protein 1 (TRP1), and dopachrome tautomerase (TRP2). We showed that the AAV6-based vaccine creates cellular and humoral antigen-specific responses, while antigen expression at the site of vaccine injection was temporal, and the clearance of antigen coincided with T cell infiltration. Our data revealed the superior protective immune response of optimized AAV6-TRP1 compared with other self-antigens in a disease-free mouse model. We further assessed the ability of AAV6-TRP1 to protect animals from metastatic spread in the lungs and to extend animal survival by inhibiting solid tumor growth. Flow cytometry-based analysis indicated significant infiltration of CD8+ T cells and natural killer (NK) cells in the tumor site, as well as changes in the polarization of intratumoral macrophages. Altogether, our data strongly support the use of optimized AAV vectors for cancer vaccine development. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2329-0501 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2329050123000086; https://doaj.org/toc/2329-0501 |
| DOI: | 10.1016/j.omtm.2023.01.006 |
| URL الوصول: | https://doaj.org/article/ffff685db9bd4576be8bb6fb095a0d7b |
| رقم الأكسشن: | edsdoj.ffff685db9bd4576be8bb6fb095a0d7b |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 23290501 |
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| DOI: | 10.1016/j.omtm.2023.01.006 |