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

Molecular Oncology

Anna Basile¹  Alessandra Rosati¹  Vincenzo De Laurenzi¹  Michelina Festa¹  Maria Caterina Turco¹  Antonia Falco¹  Luana Guerriero¹  Liberato Marzullo¹  Margot De Marco¹  Vittoria Iorio²  Daniela Eletto²  Patrizia Ballerini³  Gianluca Sala⁴  Alessia Lamolinara⁴  Verena Damiani⁴  Domenica Rea⁵  Claudio Arra⁵ 

[1] BIOUNIVERSA s.r.l. R&D Division University of Salerno Baronissi Italy;Department of Medicine, Surgery and Dentistry University of Salerno Baronissi Italy;Department of Neuroscience, Imaging and Clinical Sciences and Center for Research on Aging and Translational Medicine (CeSI‐MeT) ‘G. d'Annunzio’ University of Chieti Italy;Dipartimento di Scienze Mediche Orali e Biotecnologiche Centro Studi sull'Invecchiamento CeSI‐MeT University ‘G. d'Annunzio’ di Chieti‐Pescara Italy;S.S.D. Sperimentazione Animale Istituto Nazionale Tumori “IRCCS” Fondazione G. Pascale Naples Italy;

关键词: BAG3;    humanized antibody;    pancreatic cancer;    pancreatic ductal adenocarcinoma;    tumor therapy;   

DOI  :  10.1002/1878-0261.12492

来源: DOAJ

【 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.

【 授权许可】

Unknown