Thursday, November 21, 2024
11/21/2024
Summary Cell silicification creates cellular entities that retain the cell’s innate structure and protein features; have increased resistance to heat, pressure and dehydration; and imparts novel surface properties. The process of cryo- silicification eliminates toxic agents and creates non-viable cells that have adsorbent properties and are biodegradable, enabling in vivo antigen processing. Adsorption of pathogen-associated molecular patterns, such as monophosphoryl lipid A and CpG oligonucleotide, transforms the silicified cells into pathogen mimetics. These immunogenic cancer cells function as therapeutic vaccines that activate suppressed antigen presenting dendritic cells. Unlike previous vaccine technology using irradiated cancer cells, silicified cells do not present immune suppressive phospholipid on the cell surface and the cells are stable to dehydration, creating shelf-storable vaccines. Past clinical studies evaluating autologous and allogeneic irradiated tumor cell vaccines demonstrated safety, but failed to improve clinical outcomes. To overcome low therapeutic efficacy, we propose replacement of irradiated cancer cells with silicified cancer cells, surface masked with microbial molecules. Preclinical studies using syngeneic silicified tumor cells achieved high therapeutic efficacy in mouse models of ovarian cancer. Here we propose to evaluate the efficacy of allogeneic cancer vaccines, which are desirable based on mass production, low cost, lack of invasive procedures, and shelf-readiness. To further move towards clinical translation of the vaccine, we will evaluate human immune responses to silicified cancer vaccines using patient samples, human TLR agonists, and humanized mice. The main objectives are: 1) Determine if silicified non-syngeneic cancer vaccines are effective in mouse models of ovarian cancer and breast cancer; and 2) Validate in vivo vaccine efficacy using human cancer and immune cells.
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