Abstract LB-A14: Targeting BAG3-dependent paracrine loop reduces growth and metastatic spreading of Pancreatic adenocarcinoma

Abstract

Abstract Incidence and death rate of Pancreatic Ductal Adenocarcinoma (PDAC) has increased in recent years, therefore the identification of novel targets for treatment is extremely important. Interactions between cancer and stromal cells are critically involved in tumor formation and development of metastasis. We have recently shown (manuscript in press) that PDAC cells secrete BAG3 that binds and activates macrophages trough a specific receptor (IFITM2), inducing their activation and the secretion of PDAC supporting factors. Treatment with a murine monoclonal antibody (AC-2) targeting BAG3 reduced tumor growth and impaired metastasis formation in mouse models. Here we report further characterization of the in vivo activity of the antibody. Moreover, we have now successfully generated humanized variants of the AC-2 antibody and report the in vitro and in vivo activity of the humanized antibodies. Both appear to have the ability to inhibit macrophage activation in vitro and reduce tumor growth in PDAC models to an extent comparable to the murine parental antibody (AC-2). In conclusion, we have identified a novel paracrine loop involved in PDAC growth and metastatic spreading and shown that its pharmacological blockage with an anti-BAG3 antibody has therapeutic potential for PDAC treatment. Citation Format: Vincenzo De Laurenzi, Alessandra Rosati, Gianluca Sala, Maria Caterina Turco. Targeting BAG3-dependent paracrine loop reduces growth and metastatic spreading of Pancreatic adenocarcinoma. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-A14.