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

  • Mol Oncol. 2019 Jun;13(6):1388-1399. doi: 10.1002/1878-0261.12492.
Anna Basile  1  2 ,  Margot De Marco  1  2 ,  Michelina Festa  1  3 ,  Antonia Falco  1  3 ,  Vittoria Iorio  2 ,  Luana Guerriero  1 ,  Daniela Eletto  2 ,  Domenica Rea  4 ,  Claudio Arra  4 ,  Alessia Lamolinara  5 ,  Patrizia Ballerini  6 ,  Verena Damiani  5 ,  Alessandra Rosati  1  2 ,  Gianluca Sala  5 ,  Maria Caterina Turco  1  2 ,  Liberato Marzullo  1  2 ,  Vincenzo De Laurenzi  1  5
Affiliations
  • 1. BIOUNIVERSA s.r.l., R&D Division, University of Salerno, Baronissi, Italy.
  • 2. Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy.
  • 3. Department of Pharmacy, University of Salerno, Fisciano, Italy.
  • 4. S.S.D. Sperimentazione Animale, Istituto Nazionale Tumori "IRCCS" Fondazione G. Pascale, Naples, Italy.
  • 5. Dipartimento di Scienze Mediche, Orali e Biotecnologiche, Centro Studi sull'Invecchiamento, CeSI-MeT, University 'G. d'Annunzio' di Chieti-Pescara, Italy.
  • 6. 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.
PMID: 30973679 DOI: 10.1002/1878-0261.12492
Abstract

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.

Keywords
BAG3; humanized antibody; pancreatic cancer; pancreatic ductal adenocarcinoma; tumor therapy.
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