Characterization of A Bronchoscopically Induced Transgenic Lung Cancer Pig Model for Human Translatability

Area of Science:

• Comparative oncology
• Translational research
• Animal models in cancer

Background:

• Developing animal models with human translatability is crucial for lung cancer (LC) research.
• Pigs offer high impact for human studies due to physiological and anatomical similarities.
• A novel Oncopig model with inducible KRAS and TP53 mutations was developed for LC research.

Purpose of the Study:

• To characterize a novel, bronchoscopically-induced lung cancer (LC) model in Oncopigs.
• To assess the translatability of this Oncopig LC model to human patients.
• To compare the Oncopig LC transcriptome with human LC data.

Main Methods:

• Oncopigs underwent bronchoscopic injections and Adenovirus-Cre recombinase gene (AdCre) inductions.
• Serial contrast-enhanced chest CT scans and clinical follow-up were performed.
• Post-autopsy tissues underwent histopathology, immunohistochemistry, and RNA-sequencing for comparative analysis with human LC data.

Main Results:

• Bronchoscopic transbronchial AdCre induction resulted in a high rate of invasive cancer (91.7%) and carcinoma in situ (CIS).
• Immunohistochemistry confirmed cancer cell expression and tumor microenvironment infiltration.
• The Oncopig LC transcriptome showed significant overlap (54.3%) with human LC, surpassing that of mouse models.

Conclusions:

• The Oncopig model demonstrates a high incidence of lung cancer following bronchoscopic induction.
• Significant overlap between Oncopig and human LC transcriptomes suggests high clinical translatability.
• This immunocompetent Oncopig model is a promising tool for advancing human lung cancer research.