A CRISPR-based technology was developed to inactivate the MLH1 gene in four distinct murine cancer cell lines—CT26, MC-38, Panc02, and 4T1—yielding isogenic models that accurately mirror the microsatellite instability associated with DNA mismatch repair deficiencies. These engineered cell lines allow researchers to compare tumors with intact and defective DNA repair mechanisms under identical conditions. Notably, while MLH1 knockout cells displayed similar growth patterns to parental cells in immunocompromised mice, in immunocompetent mice the models demonstrated reduced tumor growth, increased apoptotic cell death, elevated inflammatory cytokine production, and enhanced CD8+ T lymphocyte recruitment.
Description
This technology stands out due to its precise replication of microsatellite instability effects, enabling direct investigations into the role of DNA repair deficiency in tumor immunogenicity. The striking contrast in tumor behavior between immunocompetent and immunocompromised contexts offers vital insights into the link between apoptosis and antitumor immune responses.
Applications
- Immunotherapy screening platform
- Preclinical oncology drug testing
- Personalized cancer research tool
- Immunomodulatory therapy development
Advantages
- Enables direct comparison of microsatellite stable and unstable tumors under identical conditions.
- Provides a robust model to study the role of apoptosis in triggering antitumor immune responses.
- Facilitates in-depth research into immune infiltration and cytokine regulation in MSI tumors.
- Supports preclinical studies for developing targeted immunotherapies for dMMR/MSI cancers.
- Offers a valuable platform for screening new therapeutics and advancing personalized cancer treatments.
IP Status
Research Tool
