A histone deacetylase inhibitor, panobinostat, enhances chimeric antigen receptor T-cell antitumor effect against pancreatic cancer

AI Ali; M Wang; B Von Scheidt; PM Dominguez; AJ Harrison; DGM Tantalo; J Kang; AJ Oliver; JD Chan; X Du; Y Bai; B Lee; RW Johnstone; PK Darcy; MH Kershaw; CY Slaney

Journal article

A histone deacetylase inhibitor, panobinostat, enhances chimeric antigen receptor T-cell antitumor effect against pancreatic cancer

AI Ali, M Wang, B Von Scheidt, PM Dominguez, AJ Harrison, DGM Tantalo, J Kang, AJ Oliver, JD Chan, X Du, Y Bai, B Lee, RW Johnstone, PK Darcy, MH Kershaw, CY 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

Jian Kang Author

Yuchen Bai Author

Ricky Johnstone Author

Phillip Darcy Author

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Grants

Awarded by Leukemia and Lymphoma Society

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.