Drake
William Strait

SURF Characterization and immunotherapeutic targeting of the tumor microenvironment Life Sciences

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Authors:

Drake William Strait

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Natural Killer (NK) cells are immune cells that have the capacity to target and eliminate cancer cells. Research done over the last decade has brought about significant progress in the use of NK cells in immunotherapy, particularly as we have begun to understand and exploit NK cell biology and their effector responses in tumors. NK cells are sourced from consenting donors, but this process is laborious and invasive. Alternative sources include umbilical cord blood, cell lines and induced pluripotent stem cells (iPSCs), which represent novel, and potentially allogeneic sources of NK cells. While multiple novel sourcing options exist, our understanding, as well as a direct comparison of the cytotoxicity of each source is lacking. An analysis on how effective NK from each source is at targeting tumors can provide insight on the importance of the cell's expression. In addition, how these cells perform in immunosuppressive tumor environments is unknown and is a major reason for therapy failure. This study will compare cytotoxicity of NK cells sourced from the NK-92 cell line, peripheral blood, and iPSCs genetically engineered to express chimeric antigen receptors (CARs). Cytotoxicity assays will provide a measure of the rate at which NK cells target cancer cells, allowing for a quantitative comparison between NK sources. We will, in addition, evaluate the role of oncometabolites on the proliferation of cancer cells. This research will contribute to our understanding of NK cells as immune effectors as they target difficult to kill solid tumors and inform the development of future immunotherapies. Keywords: Natural Killer Cells; Tumor Microenvironment; Oncometabolites; Induced Pluripotent Stem Cells; Chimeric Antigen Receptors

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Purdue University / 2024

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Drake William Strait