A novel intracellular nanobody against HPV16 E6 oncoprotein
Copyright © 2021 Elsevier Inc. All rights reserved.
| Publié dans: | Clinical immunology (Orlando, Fla.). - 1999. - 225(2021) vom: 01. Apr., Seite 108684 |
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| Auteur principal: | |
| Autres auteurs: | , , , |
| Format: | Article en ligne |
| Langue: | English |
| Publié: |
2021
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| Accès à la collection: | Clinical immunology (Orlando, Fla.) |
| Sujets: | Journal Article Research Support, Non-U.S. Gov't Cervical cancer E6 Human papillomavirus (HPV) Nanobody (Nb) VHH E6 protein, Human papillomavirus type 16 Oncogene Proteins, Viral Repressor Proteins |
| Résumé: | Copyright © 2021 Elsevier Inc. All rights reserved. Cervical cancer occurs as a result of the persistent infection of high-risk human papillomavirus (HPV). HPV16 oncoproteins E6 and E7 exert different and concerted pro-tumor actions in cell transformation and malignance maintenance in various m echanisms. Nanobody expressed as "intracellular antibodies" (intrabodies) can target intracellular antigens to hamper their function efficaciously and specifically. In this work, phage-display approach was employed to select the high affinity HPV16 E6-specific nanobody, nanobody Nb9 against HPV16 E6 was selected. Nb9 has high affinity (Kaff =6.3 × 108 M-) and can specifically bind endogenous HPV16 E6 protein in HPV16 positive CaSki and SiHa cells. In Nb9 overexpressed SiHa and CaSki cells, nucleus localization of HPV16 E6 was inhibited, p53 inactivation was prevented and increased apoptosis was observed. Moreover, tumor growth was inhibited in mouse xenograft model. Taken together, our results suggested that nanobody Nb9 could be a useful inhibitor for HPV16 E6 function and particularly appropriate for the treatment of HPV-associated disease |
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| Description: | Date Completed 11.06.2021 Date Revised 11.06.2021 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2021.108684 |