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

被引：19

作者：

Basile, Anna ^{[1
,2
]}

De Marco, Margot ^{[1
,2
]}

Festa, Michelina ^{[1
,3
]}

Falco, Antonia ^{[1
,3
]}

Iorio, Vittoria ^{[2
]}

Guerriero, Luana ^{[1
]}

Eletto, Daniela ^{[2
]}

Rea, Domenica ^{[4
]}

Arra, Claudio ^{[4
]}

Lamolinara, Alessia ^{[5
]}

Ballerini, Patrizia ^{[6
,7
]}

Damiani, Verena ^{[5
]}

Rosati, Alessandra ^{[1
,2
]}

Sala, Gianluca ^{[5
]}

Turco, Maria Caterina ^{[1
,2
]}

Marzullo, Liberato ^{[1
,2
]}

De Laurenzi, Vincenzo ^{[1
,5
]}

机构：

[1] Univ Salerno, R&D Div, BIOUNIVERSA Srl, Baronissi, Italy

[2] Univ Salerno, Dept Med Surg & Dent, Baronissi, Italy

[3] Univ Salerno, Dept Pharm, Fisciano, Italy

[4] Ist Nazl Tumori IRCCS Fdn G Pascale, SSD Sperimentaz Anim, Naples, Italy

[5] Univ G dAnnunzio, Ctr Studi Invecchiamento CeSI MeT, Dipartimento Sci Med Orali & Biotecnol, I-66100 Chieti, Italy

[6] Univ G dAnnunzio, Dept Neurosci Imaging & Clin Sci, Chieti, Italy

[7] Univ G dAnnunzio, Ctr Res Aging & Translat Med CeSI MeT, Chieti, Italy

来源：

MOLECULAR ONCOLOGY | 2019年 / 13卷 / 06期

关键词：

BAG3; humanized antibody; pancreatic cancer; pancreatic ductal adenocarcinoma; tumor therapy; BAG3; PROTEIN; CELL-PROLIFERATION; TUMOR-GROWTH; EXPRESSION; TARGET; ADENOCARCINOMA; CARCINOMA; SURVIVAL; FAMILY;

D O I：

10.1002/1878-0261.12492

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1388 / 1399

页数：12

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