Download or read book Strategies to Improve Natural Killer Cell Cytotoxicity Against Cancer Stem Cells written by Steven Grossenbacher and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Natural Killer cells are classically thought to be short lived effector cells capable of killing virally infected and malignantly transformed cells without prior immunization. Unlike T cells, NK cells are not restricted by specific peptide-MHC-I complexes, and thus represent a viable alternative to T cell based therapies for cancer. Recently we and others have found that NK cells can be used to target so-called cancer stem cells in in vitro and in vivo models. Cancer stem cells represent sub-populations within tumors that are resistant to conventional cyto-reductive therapies, and are capable of seeding relapse and metastasis. Therefor it is urgent to develop a means to target cancer stem cells therapeutically, in a manner that could be combined with conventional therapy. This dissertation sets out to determine how NK cell based therapies could be combined with the proteasome inhibitor bortezomib in a preclinical model system, as well as radiotherapy in a first-in-dog canine clinical trial. The goal of these studies is to understand if and how this rational combination of therapies could hold potential to target cancer stems and thus lay the foundation for clinical translation. Additionally in our first-in-dog clinical trial we assessed how the canine model could represent a viable pre-translational step to assess the efficacy and mechanism of immunotherapies in a large animal setting, prior to the human clinical scenario.