A novel fully human anti-NCL immunoRNase for triple-negative breast cancer therapy

Breast cancer is the most common cancer in women worldwide. A new promising anti-cancer therapy involves the use of monoclonal antibodies specific for target tumor-associated antigens (TAAs). A TAA of interest for immunotherapy of Triple Negative Breast Cancer (TNBC) is nucleolin (NCL), a multifunct...

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Autores principales: D'Avino, Chiara, Palmieri, Dario, Braddom, Ashley, Zanesi, Nicola, James, Cindy, Cole, Sara, Salvatore, Francesco, Croce, Carlo M., De Lorenzo, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349967/
https://www.ncbi.nlm.nih.gov/pubmed/27894092
http://dx.doi.org/10.18632/oncotarget.13522
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author D'Avino, Chiara
Palmieri, Dario
Braddom, Ashley
Zanesi, Nicola
James, Cindy
Cole, Sara
Salvatore, Francesco
Croce, Carlo M.
De Lorenzo, Claudia
author_facet D'Avino, Chiara
Palmieri, Dario
Braddom, Ashley
Zanesi, Nicola
James, Cindy
Cole, Sara
Salvatore, Francesco
Croce, Carlo M.
De Lorenzo, Claudia
author_sort D'Avino, Chiara
collection PubMed
description Breast cancer is the most common cancer in women worldwide. A new promising anti-cancer therapy involves the use of monoclonal antibodies specific for target tumor-associated antigens (TAAs). A TAA of interest for immunotherapy of Triple Negative Breast Cancer (TNBC) is nucleolin (NCL), a multifunctional protein, selectively expressed on the surface of cancer cells, which regulates the biogenesis of specific microRNAs (miRNAs) involved in tumor development and drug-resistance. We previously isolated a novel human anti-NCL scFv, called 4LB5, that is endowed with selective anti-tumor effects. Here we report the construction and characterization of a novel immunoRNase constituted by 4LB5 and a human pancreatic RNase (HP-RNase) called “4LB5-HP-RNase”. This immunoRNase retains both the enzymatic activity of human pancreatic RNase and the specific binding of the parental scFv to a panel of surface NCL-positive breast cancer cells. Notably, 4LB5-HP-RNase dramatically and selectively reduced the viability and proliferation of NCL-positive tumor cells in vitro and in vivo. Specifically, it induced apoptosis and reduced the levels of the tumorigenic miRNAs miR-21, -221 and -222. Thus, this novel immunoagent could be a valuable tool for the treatment of TNBC patients ineligible for currently available targeted treatments.
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spelling pubmed-53499672017-04-06 A novel fully human anti-NCL immunoRNase for triple-negative breast cancer therapy D'Avino, Chiara Palmieri, Dario Braddom, Ashley Zanesi, Nicola James, Cindy Cole, Sara Salvatore, Francesco Croce, Carlo M. De Lorenzo, Claudia Oncotarget Research Paper Breast cancer is the most common cancer in women worldwide. A new promising anti-cancer therapy involves the use of monoclonal antibodies specific for target tumor-associated antigens (TAAs). A TAA of interest for immunotherapy of Triple Negative Breast Cancer (TNBC) is nucleolin (NCL), a multifunctional protein, selectively expressed on the surface of cancer cells, which regulates the biogenesis of specific microRNAs (miRNAs) involved in tumor development and drug-resistance. We previously isolated a novel human anti-NCL scFv, called 4LB5, that is endowed with selective anti-tumor effects. Here we report the construction and characterization of a novel immunoRNase constituted by 4LB5 and a human pancreatic RNase (HP-RNase) called “4LB5-HP-RNase”. This immunoRNase retains both the enzymatic activity of human pancreatic RNase and the specific binding of the parental scFv to a panel of surface NCL-positive breast cancer cells. Notably, 4LB5-HP-RNase dramatically and selectively reduced the viability and proliferation of NCL-positive tumor cells in vitro and in vivo. Specifically, it induced apoptosis and reduced the levels of the tumorigenic miRNAs miR-21, -221 and -222. Thus, this novel immunoagent could be a valuable tool for the treatment of TNBC patients ineligible for currently available targeted treatments. Impact Journals LLC 2016-11-23 /pmc/articles/PMC5349967/ /pubmed/27894092 http://dx.doi.org/10.18632/oncotarget.13522 Text en Copyright: © 2016 D'Avino et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
D'Avino, Chiara
Palmieri, Dario
Braddom, Ashley
Zanesi, Nicola
James, Cindy
Cole, Sara
Salvatore, Francesco
Croce, Carlo M.
De Lorenzo, Claudia
A novel fully human anti-NCL immunoRNase for triple-negative breast cancer therapy
title A novel fully human anti-NCL immunoRNase for triple-negative breast cancer therapy
title_full A novel fully human anti-NCL immunoRNase for triple-negative breast cancer therapy
title_fullStr A novel fully human anti-NCL immunoRNase for triple-negative breast cancer therapy
title_full_unstemmed A novel fully human anti-NCL immunoRNase for triple-negative breast cancer therapy
title_short A novel fully human anti-NCL immunoRNase for triple-negative breast cancer therapy
title_sort novel fully human anti-ncl immunornase for triple-negative breast cancer therapy
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349967/
https://www.ncbi.nlm.nih.gov/pubmed/27894092
http://dx.doi.org/10.18632/oncotarget.13522
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