This product is a CRISPR/Cas9-edited polyclonal knockout cell population derived from NCI-H1975 human lung adenocarcinoma cells, featuring targeted disruption of the DPP7 gene. The polyclonal format provides a heterogeneous pool of edited cells, minimizing clonal artifacts and enabling robust functional analysis. The model serves as a loss-of-function system for investigating DPP7-dependent processes in a clinically relevant non-small cell lung cancer (NSCLC) background.
NCI-H1975 is a human lung adenocarcinoma cell line possessing activating EGFR L858R and T790M mutations, which confer resistance to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). This line is widely used to study acquired TKI resistance and to evaluate third-generation inhibitors like osimertinib. The EGFR double-mutant status makes NCI-H1975 an appropriate host for exploring interactions between oncogenic signaling and immune-related pathways.
DPP7 encodes a serine dipeptidyl peptidase that removes N-terminal Xaa-Pro dipeptides from peptide substrates. It functions critically in the endoplasmic reticulum, trimming proteasome-generated peptides to generate optimal ligands for MHC class I molecules. DPP7 activity is regulated by interferon-gamma, tumor necrosis factor-alpha, and growth factors. It works in concert with the peptide transporter TAP1/TAP2 and the aminopeptidase ERAP1 to produce stable MHC class I:peptide complexes that include beta2-microglobulin. Downstream, DPP7-processed peptides are presented as antigenic epitopes; hence, its disruption impacts antigen presentation and downstream immune recognition.
In the NCI-H1975 background, DPP7 knockout is anticipated to reduce N-terminal trimming of antigenic peptides, leading to decreased MHC class I surface expression and impaired presentation of tumor antigens. This alteration may facilitate immune evasion by the tumor cells, potentially influencing their susceptibility to T cell-mediated cytotoxicity. Given the EGFR mutation-driven oncogenic context, the model can help elucidate how compromised antigen processing intersects with TKI resistance, offering a platform to study combined therapeutic strategies.
This polyclonal knockout model is suited for cancer immunology and drug resistance research. Applications include flow cytometric measurement of MHC class I expression, T cell-mediated killing assays, and apoptosis analysis via Annexin V/PI staining. It can also be used in osimertinib sensitivity screens to evaluate how DPP7 loss affects drug response. Standard validation assays such as Western blotting and RT-qPCR confirm target disruption. For additional information, contact Ascent Research.
