This study describes the development of two immunocompetent humanized mesothelin (hMSLN) transgenic mouse lines: TPO171 and Msl. The TPO171 model exhibits thyroid-restricted hMSLN expression, while the Msl model expresses hMSLN in serosal membranes. Both models shed hMSLN into the serum, mimicking human mesothelioma and ovarian cancer patients. These models were utilized to evaluate the on-target toxicity and antitumor activity of hMSLN-targeted recombinant immunotoxins. Findings revealed that immunotoxin treatment caused histologic changes in serosal membranes in Msl mice, whereas TPO171 mice showed resistance despite effective drug delivery. Additionally, poor delivery of immunotoxin to orthotopic hMSLN-expressing pancreatic adenocarcinoma limited antitumor efficacy, even when combined with immune checkpoint inhibitors.
The study highlights the challenges in delivering complex therapeutics to pancreatic cancers, emphasizing the importance of appropriate preclinical models for evaluating hMSLN-targeted therapies.
Immunocompetent humanized mesothelin transgenic mouse models (TPO171 and Msl) expressing human mesothelin under tissue-specific promoters.
Pancreatic cancer, Immunotherapy, Mesothelin-targeted therapy, Preclinical models
Transgenic mouse models, Tissue-specific expression, Humanized antigen expression
From model design to experimental results
Tailor-made solutions adapted to scientific questions
Comprehensive dataset package
Generated with biopharma partners and in-house
Scientific follow-up and advice along the project
Collaborative approach for problem solving and development of innovative models
Breeding facilities in US and Europe
Certified health status from professional breeders
