Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/108046
DC Field | Value | Language |
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dc.contributor.author | Romano, Sofia | - |
dc.contributor.author | Moura, Vera | - |
dc.contributor.author | Simões, Sérgio | - |
dc.contributor.author | Moreira, João Nuno | - |
dc.contributor.author | Gonçalves, João | - |
dc.date.accessioned | 2023-08-07T14:27:04Z | - |
dc.date.available | 2023-08-07T14:27:04Z | - |
dc.date.issued | 2018-05-10 | - |
dc.identifier.issn | 2045-2322 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/108046 | - |
dc.description.abstract | Nucleolin arises as a relevant target for cancer therapy, as it is overexpressed at the surface of cancer and angiogenic endothelial cells thus enabling a dual cellular targeting strategy. Immunotherapeutic strategies, albeit of proven therapeutic relevance, have been scarcely explored against this target. Therefore, this work aimed at engineering an anti-nucleolin VHH-based antibody capable of triggering anticancer immune responses. Herein, anti-nucleolin VHHs have been generated upon grafting F3 peptide-derived nucleolin-binding sequences onto a VHH CDR1 or CDR3. One of these nucleolin-binding CDR3-grafted VHH was subsequently fused to a human IgG1 Fc region, enabling a significant antibody-dependent cell-mediated cytotoxicity (ADCC). The generated anti-nucleolin VHH revealed increased binding and antiproliferative effects against cancer cells, relative to the parental VHH, while the VHH-Fc counterpart presented increased cytotoxicity relative to the corresponding VHH. This VHH-Fc also triggered an ADCC effect, in the nanomolar range, against a nucleolin-overexpressing cancer cell line. This effect was evidenced by a 2 or 1.7-fold increase of cell death, in the presence of PBMCs, relative to the parental VHH-Fc or the VHH counterpart, respectively. Overall, these formats represent the first anti-nucleolin VHHs and the first anti-nucleolin antibody with ADCC activity that have been successfully developed. | pt |
dc.language.iso | eng | pt |
dc.publisher | Springer Nature | pt |
dc.relation | SFRH/BD/51680/2011 | pt |
dc.relation | POCI-01-0145-FEDER-007440 | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject.mesh | Antibody-Dependent Cell Cytotoxicity | pt |
dc.subject.mesh | Antineoplastic Agents, Immunological | pt |
dc.subject.mesh | Cell Death | pt |
dc.subject.mesh | Cell Line, Tumor | pt |
dc.subject.mesh | Humans | pt |
dc.subject.mesh | Immunoglobulin Fc Fragments | pt |
dc.subject.mesh | Immunoglobulin G | pt |
dc.subject.mesh | Immunoglobulin Heavy Chains | pt |
dc.subject.mesh | Neoplasms | pt |
dc.subject.mesh | Phosphoproteins | pt |
dc.subject.mesh | RNA-Binding Proteins | pt |
dc.subject.mesh | Single-Domain Antibodies | pt |
dc.title | Anticancer activity and antibody-dependent cell-mediated cytotoxicity of novel anti-nucleolin antibodies | pt |
dc.type | article | - |
degois.publication.firstPage | 7450 | pt |
degois.publication.issue | 1 | pt |
degois.publication.title | Scientific Reports | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1038/s41598-018-25816-8 | pt |
degois.publication.volume | 8 | pt |
dc.date.embargo | 2018-05-10 | * |
uc.date.periodoEmbargo | 0 | pt |
item.fulltext | Com Texto completo | - |
item.grantfulltext | open | - |
item.languageiso639-1 | en | - |
item.cerifentitytype | Publications | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0001-5820-9964 | - |
crisitem.author.orcid | 0000-0002-8898-7625 | - |
Appears in Collections: | FFUC- Artigos em Revistas Internacionais IIIUC - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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File | Description | Size | Format | |
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Anticancer-activity-and-antibodydependent-cellmediated-cytotoxicity-of-novel-antinucleolin-antibodiesScientific-Reports.pdf | 1.76 MB | Adobe PDF | View/Open |
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