Journal article
Eradication of solid tumors using histone deacetylase inhibitors combined with immune-stimulating antibodies
AJ Christiansen, A West, KM Banks, NM Haynes, MW Teng, MJ Smyth, RW Johnstone
Proceedings of the National Academy of Sciences of the United States of America | Published : 2011
Abstract
Histone deacetylase inhibitors (HDACi) have been successfully used as monotherapies for the treatment of hematological malignancies; however, the single agent effects of HDACi against solid tumors are less robust. Using preclinical models of lymphoma, we have recently demonstrated that HDACi induce tumor cell-specific apoptosis and that this is essential for the therapeutic effects of these agents. Herein, we demonstrate that HDACi can be combined with immune-activating antibodies designed to promote the function of antigen-presenting cells (APCs) and enhance proliferation and survival of cytotoxic T cells (CTL) to stimulate a host antitumor immune response resulting in eradication of establ..
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Funding Acknowledgements
The R.W.J. laboratory has collaborative research grants from Merck & Co and Novartis for studies involving vorinostat and panobinostat, respectively.We thank Merck & Co and Novartis for supply of vorinostat and panobinostat, respectively. R.W.J. is a Principal Research Fellow and M.J.S. is an Australian Fellow of the National Health and Medical Research Council of Australia (NHMRC). This work is supported by NHMRC program and project grants, and project grants from the Susan G. Komen for the Cure Foundation, the Victorian Breast Cancer Research Consortium, and the Prostate Cancer Foundation of Australia. A.J.C. is supported by a postdoctoral fellowship from the Cancer Council Victoria. R.W.J. is the recipient of collaborative grants from Merck and Novartis.