The CD59 Knockout AGS Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the AGS human gastric adenocarcinoma cell line. This product features targeted disruption of the CD59 gene, a key regulator of complement-mediated lysis, using CRISPR/Cas9 technology. The polyclonal pool contains a heterogeneous mixture of edited cells, allowing for the study of CD59 loss-of-function effects across a diverse genetic background. The knockout model is designed to enable investigation of complement resistance mechanisms, immune evasion, and T cell signaling in a gastric cancer context.
The AGS cell line is a human gastric adenocarcinoma line with epithelial morphology, widely used as a model for gastric cancer research, particularly in studies of H. pylori infection, cancer signaling, and chemotherapy response. These cells exhibit adherent growth and retain characteristics of gastric epithelial cells, making them a relevant host for investigating the role of complement regulatory proteins in gastric tumor biology. AGS cells are known to express components of the complement system and are susceptible to complement-dependent cytotoxicity (CDC), providing a robust background for assessing the functional impact of CD59 deficiency.
CD59 is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein that functions as a critical inhibitor of the membrane attack complex (MAC). It binds to complement components C8 and C9, preventing C9 polymerization and subsequent MAC formation, thereby protecting cells from complement-mediated lysis. In addition to its role in complement regulation, CD59 modulates T cell activation by interacting with CD2 and Src family kinases, leading to LAT phosphorylation and downstream signaling. Upstream regulators such as IL-6, TNF-alpha, and hypoxia can influence CD59 expression, while its activity directly suppresses MAC assembly. The protein is involved in multiple complement pathways, including the classical, lectin, and alternative pathways, and its dysregulation is associated with diseases like paroxysmal nocturnal hemoglobinuria and cancer immune evasion.
In the context of gastric adenocarcinoma, CD59 overexpression has been implicated in tumor immune evasion by protecting cancer cells from complement-dependent cytotoxicity and antibody-based therapies. The CD59 knockout AGS polyclonal cells provide a loss-of-function model to dissect the molecular mechanisms by which gastric cancer cells evade complement attack and to evaluate therapeutic strategies that aim to enhance complement-mediated tumor cell killing. By disrupting CD59 in an epithelial gastric cancer background, researchers can study how the absence of this regulator affects MAC sensitivity, T cell signaling crosstalk, and the interplay between complement activation and cancer cell survival.
These polyclonal knockout cells are ideal for a range of experimental applications, including flow cytometry-based analysis of MAC deposition and complement regulatory protein expression, complement-dependent cytotoxicity assays to measure cell lysis sensitivity, and Western blotting or RT-qPCR to verify CD59 disruption and downstream signaling effects. The model enables investigation of how loss of CD59 influences T cell activation through LAT and Src kinase pathways, as well as studies on enhancing antibody-mediated cancer therapies by sensitizing tumor cells to complement. For ordering information, custom bulk orders, or technical inquiries, please contact Ascent Research.
