BioCentury
ARTICLE | Distillery Therapeutics

Cancer

August 9, 2017 6:41 PM UTC

Patient sample, cell culture and mouse studies suggest inhibiting HDAC1 alone or in combination with T cell therapies could help treat NANOG-positive cervical and breast cancers. In cervical cancer patient samples, high tumor levels of HDAC1 correlated with high tumor levels of NANOG and disease progression, and the high tumor levels of HDAC1 and NANOG were associated with poor overall survival. In a human cervical cancer cell line resistant to cytotoxic T cells, levels of HDAC1 and NANOG were higher than in a cytotoxic T cell-sensitive version of the cell line. In a NANOG-overexpressing human cervical cancer cell line, HDAC1 knockdown decreased tumorsphere formation and increased levels of GrB-dependent apoptosis, a marker of cytotoxic T cell susceptibility, compared with normal HDAC1 expression. In a xenograft mouse model of NANOG-overexpressing cervical cancer, knockdown of HDAC1 decreased tumor size and the incidence of tumor formation. In a xenograft mouse model of NANOG-expressing breast cancer, the HDAC inhibitor Istodax romidepsin plus adoptive transfer of tumor-specific human cytotoxic T cells decreased tumor size and increased tumor cell apoptosis and survival compared with either strategy alone. Next steps could include testing HDAC1 inhibition in combination with other T cell-based therapies in models of NANOG-positive cervical and breast cancers...