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Development of an anti‐BAG3 humanized antibody for treatment of pancreatic cancer

We have previously shown that secreted BAG3 is a potential target for the treatment of pancreatic ductal adenocarcinoma and that pancreatic tumor growth and metastatic dissemination can be reduced by treatment with an anti‐BAG3 murine antibody. Here, we used complementarity‐determining region (CDR)...

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Autores principales: Basile, Anna, De Marco, Margot, Festa, Michelina, Falco, Antonia, Iorio, Vittoria, Guerriero, Luana, Eletto, Daniela, Rea, Domenica, Arra, Claudio, Lamolinara, Alessia, Ballerini, Patrizia, Damiani, Verena, Rosati, Alessandra, Sala, Gianluca, Turco, Maria Caterina, Marzullo, Liberato, De Laurenzi, Vincenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547619/
https://www.ncbi.nlm.nih.gov/pubmed/30973679
http://dx.doi.org/10.1002/1878-0261.12492
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author Basile, Anna
De Marco, Margot
Festa, Michelina
Falco, Antonia
Iorio, Vittoria
Guerriero, Luana
Eletto, Daniela
Rea, Domenica
Arra, Claudio
Lamolinara, Alessia
Ballerini, Patrizia
Damiani, Verena
Rosati, Alessandra
Sala, Gianluca
Turco, Maria Caterina
Marzullo, Liberato
De Laurenzi, Vincenzo
author_facet Basile, Anna
De Marco, Margot
Festa, Michelina
Falco, Antonia
Iorio, Vittoria
Guerriero, Luana
Eletto, Daniela
Rea, Domenica
Arra, Claudio
Lamolinara, Alessia
Ballerini, Patrizia
Damiani, Verena
Rosati, Alessandra
Sala, Gianluca
Turco, Maria Caterina
Marzullo, Liberato
De Laurenzi, Vincenzo
author_sort Basile, Anna
collection PubMed
description We have previously shown that secreted BAG3 is a potential target for the treatment of pancreatic ductal adenocarcinoma and that pancreatic tumor growth and metastatic dissemination can be reduced by treatment with an anti‐BAG3 murine antibody. Here, we used complementarity‐determining region (CDR) grafting to generate a humanized version of the anti‐BAG3 antibody that may be further developed for possible clinical use. We show that the humanized anti‐BAG3 antibody, named BAG3‐H2L4, abrogates BAG3 binding to macrophages and subsequent release of IL‐6. Furthermore, it specifically localizes into tumor tissues and significantly inhibits the growth of Mia PaCa‐2 pancreatic cancer cell xenografts. We propose BAG3‐H2L4 antibody as a potential clinical candidate for BAG3‐targeted therapy in pancreatic cancer.
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spelling pubmed-65476192019-06-06 Development of an anti‐BAG3 humanized antibody for treatment of pancreatic cancer Basile, Anna De Marco, Margot Festa, Michelina Falco, Antonia Iorio, Vittoria Guerriero, Luana Eletto, Daniela Rea, Domenica Arra, Claudio Lamolinara, Alessia Ballerini, Patrizia Damiani, Verena Rosati, Alessandra Sala, Gianluca Turco, Maria Caterina Marzullo, Liberato De Laurenzi, Vincenzo Mol Oncol Research Articles We have previously shown that secreted BAG3 is a potential target for the treatment of pancreatic ductal adenocarcinoma and that pancreatic tumor growth and metastatic dissemination can be reduced by treatment with an anti‐BAG3 murine antibody. Here, we used complementarity‐determining region (CDR) grafting to generate a humanized version of the anti‐BAG3 antibody that may be further developed for possible clinical use. We show that the humanized anti‐BAG3 antibody, named BAG3‐H2L4, abrogates BAG3 binding to macrophages and subsequent release of IL‐6. Furthermore, it specifically localizes into tumor tissues and significantly inhibits the growth of Mia PaCa‐2 pancreatic cancer cell xenografts. We propose BAG3‐H2L4 antibody as a potential clinical candidate for BAG3‐targeted therapy in pancreatic cancer. John Wiley and Sons Inc. 2019-05-17 2019-06 /pmc/articles/PMC6547619/ /pubmed/30973679 http://dx.doi.org/10.1002/1878-0261.12492 Text en © 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Basile, Anna
De Marco, Margot
Festa, Michelina
Falco, Antonia
Iorio, Vittoria
Guerriero, Luana
Eletto, Daniela
Rea, Domenica
Arra, Claudio
Lamolinara, Alessia
Ballerini, Patrizia
Damiani, Verena
Rosati, Alessandra
Sala, Gianluca
Turco, Maria Caterina
Marzullo, Liberato
De Laurenzi, Vincenzo
Development of an anti‐BAG3 humanized antibody for treatment of pancreatic cancer
title Development of an anti‐BAG3 humanized antibody for treatment of pancreatic cancer
title_full Development of an anti‐BAG3 humanized antibody for treatment of pancreatic cancer
title_fullStr Development of an anti‐BAG3 humanized antibody for treatment of pancreatic cancer
title_full_unstemmed Development of an anti‐BAG3 humanized antibody for treatment of pancreatic cancer
title_short Development of an anti‐BAG3 humanized antibody for treatment of pancreatic cancer
title_sort development of an anti‐bag3 humanized antibody for treatment of pancreatic cancer
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547619/
https://www.ncbi.nlm.nih.gov/pubmed/30973679
http://dx.doi.org/10.1002/1878-0261.12492
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