A Histone Deacetylase Inhibitor, Panobinostat, Enhances Chimeric Antigen Receptor T-cell Antitumor Effect Against Pancreatic Cancer.
Aesha I Ali, Minyu Wang, Bianca von Scheidt, Pilar M Dominguez, Aaron J Harrison, Daniela Gm Tantalo, Jian Kang, Amanda J Oliver, Jack D Chan, Xin Du, Yuchen Bai, Belinda Lee, Ricky W Johnstone, Phillip K Darcy, Michael H Kershaw, Clare Y Slaney
Clin Cancer Res | Published : 2021
PURPOSE: In this article, we describe a combination chimeric antigen receptor (CAR) T-cell therapy that eradicated the majority of tumors in two immunocompetent murine pancreatic cancer models and a human pancreatic cancer xenograft model. EXPERIMENTAL DESIGN: We used a dual-specific murine CAR T cell that expresses a CAR against the Her2 tumor antigen, and a T-cell receptor (TCR) specific for gp100. As gp100 is also known as pMEL, the dual-specific CAR T cells are thus denoted as CARaMEL cells. A vaccine containing live vaccinia virus coding a gp100 minigene (VV-gp100) was administered to the recipient mice to stimulate CARaMEL cells. The treatment also included the histone deacetylase inhi..View full abstract
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