The Inhibitory Effects of Anti-ERC/Mesothelin Antibody 22A31 on Colorectal Adenocarcinoma Cells, within a Mouse Xenograft Model

SIMPLE SUMMARY: The expression of Renal Carcinoma (ERC)/mesothelin is overexpressed in malignancies such as mesothelioma, pancreatic cancer, and ovarian cancer, and molecular-targeted therapies against ERC/mesothelin have been developed to treat them. Recently, it was revealed that ERC/mesothelin is also expressed in colorectal cancer; thus, this protein is expected to be a therapeutic target in colorectal cancer. In this study, we demonstrated that anti-ERC/mesothelin antibody 22A31 suppressed the growth of colorectal cancer cells subcutaneously xenografted on the back of mice. This is the first report to show the effectiveness of an anti-ERC/mesothelin antibody for the treatment of colorectal cancer in vivo. 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.