A pan inhibitor of DASH family enzymes induces immunogenic modulation and sensitizes murine and human carcinoma cells to antigen-specific cytotoxic T lymphocyte killing: implications for combination therapy with cancer vaccines |
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| Authors: | Renee N. Donahue Brynn B. Duncan Terry J. Fry Barry Jones William W. Bachovchin Christopher P. Kiritsy Jack H. Lai Wengen Wu Peng Zhao Yuxin Liu Kwong-Yok Tsang James W. Hodge |
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| Affiliation: | 1. Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA;2. Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA;3. Department of Biochemistry, Tufts University School of Medicine, Boston, MA, USA;4. Arisaph Pharmaceuticals, Boston, MA, USA |
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| Abstract: | Recent studies have suggested that pan inhibitors of dipeptidyl peptidase-4 activity and/or structure homologs (DASH), including ARI-4175, can mediate tumor regression by immune-mediated mechanisms. This study assessed the potential of combining ARI-4175 with cancer vaccines. We evaluated ARI-4175's effect on immunogenic modulation, ability to sensitize tumor cells to antigen-specific CTL killing, effect on immune-cell subsets and function, and antitumor activity in 2 tumor models, both as a monotherapy and in combination with a recombinant viral or dendritic cell (DC)-based tumor-cell vaccine. |
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| Keywords: | Immunogenic modulation T-cell response DASH family enzymes Immunotherapy Vaccine |
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