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

Our plain-English summary of The Inhibitory Effects of Anti-ERC/Mesothelin Antibody 22A31 on Colorectal Adenocarcinoma Cells, within a Mouse Xenograft Model, by G. Taniguchi, K. Kajino, S. Momose, et al (Cancers, 2022).

The study

• Authors: G. Taniguchi, K. Kajino, S. Momose, H. Saeki, L. Yue, N. Ohtsuji, M. Abe, T. Shibuya, A. Orimo, A. Nagahara, S. Watanabe, O. Hino
• Journal: Cancers
• Published: 2022;14(9)
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This laboratory experiment in mice did not study asbestos. The authors tested whether 22A31, their antibody against ERC/mesothelin, could slow human colorectal (bowel) cancer growth. HCT116 human colorectal adenocarcinoma cells were injected under the skin of ten female nude mice. Five mice were assigned to 22A31 and five to a control antibody, planned twice weekly for 4 weeks. One control mouse died on Day 20. On Day 29, tumors in the 22A31 group were significantly smaller than in the control group. They also had fewer dividing cells (p less than 0.05). In lab-dish tests, the antibody did not change the cell cycle or a measure of cell death. In the tumors, two cell-death markers showed no significant group difference; the authors noted earlier cell death could have gone undetected. Lung micro-metastases were found in three of five treated mice and two of four control mice, with no significant difference. The authors said five mice per group was not enough for firm conclusions about cell death. They concluded that ERC/mesothelin-targeted therapy might be a promising treatment for colorectal cancer.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment (mouse xenograft model, in which human cancer cells are grown in mice), with additional cell-culture (in vitro) tests
• Who was studied: Ten female BALB/c athymic nude mice, 7 to 8 weeks old, injected with human colorectal adenocarcinoma cells (HCT116). Five mice were assigned to each group. Juntendo University, Tokyo, Japan.
• Exposure: No asbestos exposure was studied. The treatment was the anti-ERC/mesothelin antibody 22A31 or a control antibody (IgG1κ), 200 µg per mouse, injected into the abdomen. The protocol was twice a week for 4 weeks, starting once tumors exceeded 40 mm3.
• Main results:
  • One control-group mouse died on Day 20. All five mice in the 22A31 group and four in the control group completed the protocol.
  • On Day 29, tumors in the 22A31-treated mice were significantly smaller than tumors in the control-antibody mice.
  • Tumors in the control group had a significantly higher Ki-67 labeling index (a measure of dividing cells) than tumors in the 22A31 group (p less than 0.05).
  • In lab-dish tests, 22A31 did not change the cell cycle of HCT116 cells.
  • In lab-dish tests, 22A31 did not change Annexin-V positivity (a measure of cell death) in HCT116 cells.
  • In the tumors, cleaved caspase 3 staining (a cell-death marker) showed no significant difference between the two groups.
  • In the tumors, the TUNEL assay (another cell-death marker) showed no significant difference between the two groups.
  • No liver metastases were found. Lung micro-metastases were found in 3 of 5 mice in the 22A31 group and 2 of 4 mice in the control group, with no significant difference.
• The authors' conclusion: The authors concluded that their results implied ERC/mesothelin-targeted therapy might be a promising treatment for colorectal cancer.
• Limitations the authors state:
  • A single experiment with five mice per group was not enough for rigorous conclusions about the role of cell death (apoptosis).
  • Tumor cell death caused by the antibody could have happened earlier than the point when the mice were examined, and so gone undetected.
  • There were too few metastases to analyze statistically.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelin, Adenocarcinoma, Carcinoma, Apoptosis, Mesothelioma, Ovarian Cancer, Colorectal Cancer, Immunohistochemistry.

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• Antitumor activity of anti-C-ERC/mesothelin monoclonal antibody in vivo — K. Inami, M. Abe, et al. (2010)
• Malignant Mesothelioma Effusions Are Infiltrated by CD3+ T Cells Highly Expressing PD-L1 and the PD-L1+ Tumor Cells within These Effusions Are Susceptible to ADCC by the Anti-PD-L1 Antibody Avelumab — S. Khanna, A. Thomas, et al. (2016)
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• Anti-PD1 does not improve pyroptosis induced by γδ T cells but promotes tumor regression in a pleural mesothelioma mouse model — K.S. Lui, Z. Ye, et al. (2023)

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