Anticancer activity and antibody-dependent cell-mediated cytotoxicity of novel anti-nucleolin antibodies

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 agai...

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Autores principales:	Sofia Romano, Vera Moura, Sérgio Simões, João Nuno Moreira, João Gonçalves
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1e57d1ee92984485a418010f2f6800b3
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spelling	oai:doaj.org-article:1e57d1ee92984485a418010f2f6800b32021-12-02T16:07:50ZAnticancer activity and antibody-dependent cell-mediated cytotoxicity of novel anti-nucleolin antibodies10.1038/s41598-018-25816-82045-2322https://doaj.org/article/1e57d1ee92984485a418010f2f6800b32018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25816-8https://doaj.org/toc/2045-2322Abstract 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.Sofia RomanoVera MouraSérgio SimõesJoão Nuno MoreiraJoão GonçalvesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sofia Romano Vera Moura Sérgio Simões João Nuno Moreira João Gonçalves Anticancer activity and antibody-dependent cell-mediated cytotoxicity of novel anti-nucleolin antibodies
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.
format	article
author	Sofia Romano Vera Moura Sérgio Simões João Nuno Moreira João Gonçalves
author_facet	Sofia Romano Vera Moura Sérgio Simões João Nuno Moreira João Gonçalves
author_sort	Sofia Romano
title	Anticancer activity and antibody-dependent cell-mediated cytotoxicity of novel anti-nucleolin antibodies
title_short	Anticancer activity and antibody-dependent cell-mediated cytotoxicity of novel anti-nucleolin antibodies
title_full	Anticancer activity and antibody-dependent cell-mediated cytotoxicity of novel anti-nucleolin antibodies
title_fullStr	Anticancer activity and antibody-dependent cell-mediated cytotoxicity of novel anti-nucleolin antibodies
title_full_unstemmed	Anticancer activity and antibody-dependent cell-mediated cytotoxicity of novel anti-nucleolin antibodies
title_sort	anticancer activity and antibody-dependent cell-mediated cytotoxicity of novel anti-nucleolin antibodies
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/1e57d1ee92984485a418010f2f6800b3
work_keys_str_mv	AT sofiaromano anticanceractivityandantibodydependentcellmediatedcytotoxicityofnovelantinucleolinantibodies AT veramoura anticanceractivityandantibodydependentcellmediatedcytotoxicityofnovelantinucleolinantibodies AT sergiosimoes anticanceractivityandantibodydependentcellmediatedcytotoxicityofnovelantinucleolinantibodies AT joaonunomoreira anticanceractivityandantibodydependentcellmediatedcytotoxicityofnovelantinucleolinantibodies AT joaogoncalves anticanceractivityandantibodydependentcellmediatedcytotoxicityofnovelantinucleolinantibodies
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Anticancer activity and antibody-dependent cell-mediated cytotoxicity of novel anti-nucleolin antibodies

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