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Novel mouse model for carcinoembryonic antigen-based therapy
Carlos H F Chan1, Clifford P Stanners
1Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, Quebec, Canada H3G 1Y6.
Abstract:
Many novel cancer therapies, including immunotherapy and gene therapy, are specifically targeted to tumor-associated molecules, among which carcinoembryonic antigen (CEA) represents a popular example. Discrepancies between preclinical experimental data in animal models and clinical outcome in terms of therapeutic response and toxicity, however, often arise. Preclinical testing can be compromised by the lack of CEA and other closely related human CEA family members in rodents, which lack analogous genes for most human CEA family members. Here, we report the construction of a transgenic mouse with a 187-kb human bacterial artificial chromosome (CEABAC) that contains part of the human CEA family gene cluster including complete human CEA (CEACAM5), CEACAM3, CEACAM6, and CEACAM7 genes. The spatiotemporal expression pattern of these genes in the CEABAC mice was found to be remarkably similar to that of humans. This novel mouse will ensure better assessment than previously utilized models for the preclinical testing of CEA-targeted therapies and perhaps allow the testing of CEACAM6, which is overexpressed in many solid tumors and leukemias, as a therapeutic target. Moreover, expression of CEA family genes in gastrointestinal, breast, hematopoietic, urogenital, and respiratory systems could facilitate other clinical applications, such as the development of therapeutic agents against Neisseria gonorrhoeae infections, which use CEA family members as major receptors.
Insights
Researchers developed a novel transgenic mouse model containing human carcinoembryonic antigen (CEA) family genes. This CEABAC mouse allows for more accurate preclinical testing of CEA-targeted cancer therapies and other applications.
Area of Science:
- Oncology
- Genetics
- Immunology
Background:
- Novel cancer therapies like immunotherapy target tumor-associated molecules such as carcinoembryonic antigen (CEA).
- Existing animal models often fail to accurately predict clinical outcomes due to a lack of human CEA family genes in rodents.
- This discrepancy hinders the development and efficacy testing of targeted cancer treatments.
Purpose of the Study:
- To create a transgenic mouse model that accurately expresses human CEA family genes.
- To enable more reliable preclinical evaluation of CEA-targeted therapies.
- To explore new therapeutic targets and applications for CEA family genes.
Main Methods:
- Construction of a 187-kb human bacterial artificial chromosome (CEABAC) containing key human CEA family genes (CEACAM5, CEACAM3, CEACAM6, CEACAM7).
- Generation of CEABAC transgenic mice.
- Analysis of the spatiotemporal expression patterns of the introduced human genes in the mouse model.
Main Results:
- The CEABAC mice successfully express human CEA family genes.
- The expression pattern of these genes in CEABAC mice closely mimics human expression.
- This model provides a superior platform for preclinical assessment of CEA-targeted therapies.
Conclusions:
- The CEABAC mouse model offers a significant advancement for preclinical testing of cancer therapies targeting carcinoembryonic antigen (CEA).
- This model facilitates the evaluation of CEACAM6 as a potential therapeutic target in various cancers.
- Potential applications extend to developing treatments for infections, such as Neisseria gonorrhoeae, that utilize CEA family receptors.
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