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The Inhibitory Effects of Anti-ERC/Mesothelin Antibody 22A31 on Colorectal Adenocarcinoma Cells, within a Mouse
Gentaro Taniguchi1,2, Kazunori Kajino1,3, Shuji Momose4
1Department of Molecular Pathology, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Abstract:
The expression of Renal Carcinoma (ERC)/mesothelin is enhanced in a variety of cancers. ERC/mesothelin contributes to cancer progression by modulating cell signals that regulate proliferation and apoptosis. Based on such biological insights, ERC/mesothelin has become a molecular target for the treatment of mesothelioma, pancreatic cancer, and ovarian cancer. Recent studies revealed about 50-60% of colorectal adenocarcinomas also express ERC/mesothelin. Therefore, colorectal cancer can also be a potential target of the treatment using an anti-ERC/mesothelin antibody. We previously demonstrated an anti-tumor effect of anti-ERC antibody 22A31 against mesothelioma. In this study, we investigated the effect of 22A31 on a colorectal adenocarcinoma cell line, HCT116. The cells were xenografted into BALB/c nu/nu mice. All mice were randomly allocated to either an antibody treatment group with 22A31 or isotype-matched control IgG1κ. We compared the volume of subsequent tumors, and tumors were pathologically assessed by immunohistochemistry. Tumors treated with 22A31 were significantly smaller than those treated with IgG1κ and contained significantly fewer mitotic cells with Ki67 staining. We demonstrated that 22A31 exhibited a growth inhibitory property on HCT116. Our results implied that ERC/mesothelin-targeted therapy might be a promising treatment for colorectal cancer.
Insights
An anti-Equity-Related Concepts (ERC)/mesothelin antibody, 22A31, significantly reduced colorectal tumor growth in mice. This suggests ERC/mesothelin-targeted therapy is a promising new treatment for colorectal cancer.
Area of Science:
- Oncology
- Immunotherapy
Background:
- Equity-Related Concepts (ERC)/mesothelin is overexpressed in various cancers, including mesothelioma, pancreatic, and ovarian cancers.
- Recent findings indicate 50-60% of colorectal adenocarcinomas also express ERC/mesothelin, identifying it as a potential therapeutic target.
- Previous studies demonstrated the anti-tumor efficacy of the anti-ERC antibody 22A31 in mesothelioma models.
Purpose of the Study:
- To investigate the anti-tumor effect of the anti-ERC antibody 22A31 on colorectal adenocarcinoma cells (HCT116).
- To evaluate the potential of ERC/mesothelin-targeted therapy for colorectal cancer treatment.
Main Methods:
- HCT116 colorectal adenocarcinoma cells were xenografted into BALB/c nu/nu mice.
- Mice were treated with either the anti-ERC antibody 22A31 or an isotype-matched control IgG1κ.
- Tumor volume and pathological features (immunohistochemistry for Ki67) were assessed.
Main Results:
- Treatment with 22A31 resulted in significantly smaller tumors compared to the control group.
- Tumors from the 22A31 treatment group showed significantly fewer mitotic cells, as indicated by Ki67 staining.
- The antibody 22A31 demonstrated a clear growth inhibitory effect on HCT116 cells.
Conclusions:
- The anti-ERC antibody 22A31 exhibits significant anti-tumor activity against colorectal adenocarcinoma.
- Targeting ERC/mesothelin with antibodies like 22A31 represents a promising therapeutic strategy for colorectal cancer.
