The SRG rat, a Sprague-Dawley Rag2/Il2rg double-knockout validated for human tumor oncology studies

Area of Science:

• Immunology
• Oncology
• Animal Models

Background:

• Existing immunodeficient rodent models exhibit limitations in engraftment and growth for certain human cancer cell lines and patient-derived xenografts (PDXs).
• Specific models like VCaP prostate cancer show poor reliability in conventional models.
• Rats offer potential for larger tumor volumes compared to mice, beneficial for PDX development.

Purpose of the Study:

• To introduce and validate the immunodeficient SRG rat (Sprague-Dawley Rag2/Il2rg double knockout) as a superior model for oncology research.
• To assess the SRG rat's efficacy in engrafting and growing human cancer cell lines and PDXs.
• To evaluate the SRG rat as a platform for establishing robust PDX banks.

Main Methods:

• Creation of the SRG rat, a double knockout lacking mature B cells, T cells, and NK cells.
• Testing SRG rats with human cancer cell lines (e.g., VCaP) and patient-derived non-small cell lung cancer (NSCLC) tissues.
• Molecular and histological analyses of PDX lines across multiple passages to ensure fidelity to original samples.

Main Results:

• SRG rats demonstrated high tumor take rates (>90% for VCaP) and consistent growth kinetics.
• Successful engraftment of 78% of NSCLC patient tissues, yielding large tumor volumes (>20,000 mm3) in the first passage.
• High concordance in molecular and histological profiles between PDX passages and original patient samples.

Conclusions:

• The SRG OncoRat is a highly effective model for human cancer cell line and PDX xenografts, surpassing limitations of current models.
• Its high engraftment rates and rapid, uniform tumor growth facilitate efficient PDX bank establishment.
• The SRG rat offers a valuable alternative for preclinical oncology studies and biobanking, supporting larger tumor development and tissue availability.