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https://hdl.handle.net/10316/108046
Title: | Anticancer activity and antibody-dependent cell-mediated cytotoxicity of novel anti-nucleolin antibodies | Authors: | Romano, Sofia Moura, Vera Simões, Sérgio Moreira, João Nuno Gonçalves, João |
Issue Date: | 10-May-2018 | Publisher: | Springer Nature | Project: | SFRH/BD/51680/2011 POCI-01-0145-FEDER-007440 |
Serial title, monograph or event: | Scientific Reports | Volume: | 8 | Issue: | 1 | 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. | URI: | https://hdl.handle.net/10316/108046 | ISSN: | 2045-2322 | DOI: | 10.1038/s41598-018-25816-8 | Rights: | openAccess |
Appears in Collections: | FFUC- Artigos em Revistas Internacionais IIIUC - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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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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