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Updated: Jan 21, 2026
Orthotopic Mouse Model of Colorectal Cancer
Published on: December 4, 2007
Anti-Mesothelin Recombinant Immunotoxin Therapy for Colorectal Cancer
Adam Cerise1, Tapan K Bera1, Xiufen Liu1
1Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
Background:
Mesothelin (MSLN) is a cell surface glycoprotein expressed at a high level on many malignancies, including pancreatic adenocarcinoma, serous ovarian cancer, and epithelioid mesothelioma. MSLN-targeted recombinant immunotoxins (RITs) consist of an anti-MSLN Fv fused to the catalytic domain of Pseudomonas exotoxin A. Recent data has also shown that MSLN is expressed at clinically relevant levels on the surface of colorectal cancer (CRC). In this study, CRC cell lines were tested for MSLN expression and susceptibility to MSLN-targeted RITs.
Materials And Methods:
CRC cell lines were tested for membranous MSLN expression via flow cytometry. Cell lines expressing MSLN were tested by WST-8 cell viability assay for sensitivity to various RITs and chemotherapeutic agents. CRC cell line SW-48 was tested in a mouse model for response to RIT as a single agent or in combination with actinomycin D and oxaliplatin.
Results:
CRC cell lines were susceptible to anti-MSLN RITs at half maximal inhibitory concentration levels comparable with those previously described in pancreatic cancer cell lines. In a nude mouse model, MSLN-targeted RIT treatment of SW48 CRC tumors resulted in a significant decrease in tumor volume. Although combination therapy with standard of care chemotherapeutic oxaliplatin did not improve tumor regressions, combination therapy with actinomycin D resulted in > 90% tumor volume reduction with 50% complete regressions.
Conclusions:
These data support the development of anti-MSLN RITs as well as other MSLN-targeted therapies for CRC.
Insights
Mesothelin (MSLN)-targeted immunotoxins show promise for colorectal cancer (CRC) treatment. In preclinical models, these therapies significantly reduced tumor volume, with combination treatments yielding substantial regressions.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Biology
Background:
- Mesothelin (MSLN) is a cell surface glycoprotein highly expressed in various cancers, including pancreatic adenocarcinoma, ovarian cancer, and mesothelioma.
- Recent findings indicate MSLN expression in colorectal cancer (CRC) at clinically relevant levels.
- MSLN-targeted recombinant immunotoxins (RITs) are novel therapeutic agents comprising an anti-MSLN Fv fragment linked to Pseudomonas exotoxin A.
Purpose of the Study:
- To evaluate the expression of MSLN in colorectal cancer (CRC) cell lines.
- To assess the susceptibility of MSLN-expressing CRC cells to MSLN-targeted RITs.
- To investigate the efficacy of MSLN-targeted RITs in a preclinical mouse model of CRC.
Main Methods:
- Membranous MSLN expression in CRC cell lines was quantified using flow cytometry.
- Cell viability assays (WST-8) were employed to determine sensitivity to RITs and chemotherapeutic agents.
- The SW-48 CRC cell line was utilized in a mouse model to assess RIT efficacy as a single agent and in combination therapies.
Main Results:
- CRC cell lines demonstrated susceptibility to anti-MSLN RITs, with inhibitory concentrations comparable to those in pancreatic cancer cell lines.
- Treatment with MSLN-targeted RITs led to a significant reduction in tumor volume in the SW48 mouse model.
- Combination therapy with actinomycin D resulted in over 90% tumor volume reduction and 50% complete regressions, while oxaliplatin combination showed no improvement.
Conclusions:
- The findings support the development of anti-MSLN RITs for colorectal cancer (CRC) treatment.
- MSLN-targeted therapies represent a promising therapeutic strategy for CRC.
- Further investigation into MSLN-targeted immunotoxins for CRC is warranted based on preclinical efficacy.
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