We have previously shown that secreted BAG3 is a potential target for 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 MiaPaCa-2 pancreatic cancer cell xenografts. We propose BAG3-H2L4 antibody as a potential clinical candidate for BAG3-targeted therapy in pancreatic cancer.

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

De Marco Agrosi', Martina;Lamolinara A;Ballerini P;Damiani V;Sala G;TURCO, MARIA CATERINA;De Laurenzi V
2019

Abstract

We have previously shown that secreted BAG3 is a potential target for 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 MiaPaCa-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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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11564/703067
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