A Histone Deacetylase Inhibitor, Panobinostat, Enhances Chimeric Antigen Receptor T-cell Antitumor Effect Against Pancreatic Cancer

Aesha 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

Journal article

A Histone Deacetylase Inhibitor, Panobinostat, Enhances Chimeric Antigen Receptor T-cell Antitumor Effect Against Pancreatic Cancer

Aesha 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

CLINICAL CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2021

DOI: 10.1158/1078-0432.CCR-21-1141

Abstract

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..

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University of Melbourne Researchers

Phillip Darcy Author The Sir Peter Maccallum Department of Oncology

Clare Slaney Author The Sir Peter Maccallum Department of Oncology

Jian Kang Author The Sir Peter Maccallum Department of Oncology

Ricky Johnstone Author The Sir Peter Maccallum Department of Oncology

Belinda Lee Author Medical Biology (w.e.h.i.)

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Grants

Awarded by National Health and Medical Research Council (NHMRC) of Australia

Awarded by National Breast Cancer Foundation (NBCF) of Australia

Awarded by Susan G. Komen Breast Cancer Foundation

Funding Acknowledgements

The authors would like to acknowledge the assistance from the Peter MacCallum Cancer Centre animal facility and Centre for Advanced Histology and Microscopy. This work was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia (1103352, 1132373, 1136680, and 1176935) the National Breast Cancer Foundation (NBCF) of Australia (IIRS-18-064 and IIRS-20-073) and Susan G. Komen Breast Cancer Foundation (16376637). R.W. Johnstone was supported by the Cancer Council Victoria, NHMRC, the Leukemia and Lymphoma Society, the Snowdome Foundation and the Kids' Cancer Project.