Ganetespib, an HSP90 inhibitor, kills Epstein–Barr virus (EBV)-infected B and T cells and reduces the percentage of EBV-infected cells in the blood

Abstract

HSP90 inhibitors have been shown to kill Epstein–Barr virus (EBV)-infected cells by reducing the level of EBV EBNA-1 and/or LMP1. We treated virus-infected cells with ganetespib, an HSP90 inhibitor currently being evaluated in multiple clinical trials for cancer and found that the drug killed EBV-positive B and T cells and reduced the level of both EBV EBNA-1 and LMP1. Treatment of cells with ganetespib also reduced the level of pAkt. Ganetespib delayed the onset of EBV-positive lymphomas and prolonged survival in SCID mice inoculated with one EBV-transformed B-cell line, but not another B-cell line. The former cell line showed lower levels of EBNA-1 after treatment with ganetespib in vitro. Treatment of a patient with T-cell chronic active EBV with ganetespib reduced the percentage of EBV-positive cells in the peripheral blood. These data indicate that HSP90 inhibitors may have a role in the therapy of certain EBV-associated diseases.

Keywords:

• Ganetespib
• HSP90
• Epstein–Barr virus
• Burkitt’s lymphoma

Acknowledgements

This work was supported by the intramural research programs of the National Institute of Allergy and Infectious Diseases and the National Cancer Institute. We thank Robert Bradley (Synta Pharmaceuticals) for planning and oversight of our clinical study, Jeffery Sample (Pennsylvania State University College of Medicine) for Mutu I, Kem I, and Akata cell lines, Paul Ling (Baylor College of Medicine) and Norio Shimizu (Tokyo Medical and Dental University) for SNT16 cells, Anita Mora (Rocky Mountain Laboratory, NIH) for preparing figures, and Harlan Pietz (Laboratory of Infectious Diseases, NIH) for statistical analyses.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.1080/10428194.2016.1213823.