Novel mouse model for carcinoembryonic antigen-based therapy

Carlos H F Chan; Clifford P Stanners

doi:10.1016/j.ymthe.2004.03.009

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Novel mouse model for carcinoembryonic antigen-based therapy

Journal article

Open access

Peer reviewed

Novel mouse model for carcinoembryonic antigen-based therapy

Carlos H F Chan and Clifford P Stanners

Molecular therapy, Vol.9(6), pp.775-785

06/2004

DOI: 10.1016/j.ymthe.2004.03.009

PMID: 15194045

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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.

Multigene Family - genetics

Antigens, Neoplasm - genetics

Cell Adhesion Molecules - genetics

Gene Expression

Humans

GPI-Linked Proteins

Carcinoembryonic Antigen - genetics

Mice, Transgenic - genetics

Carcinoembryonic Antigen - analysis

Chromosomes, Artificial, Bacterial - genetics

Tissue Distribution

Animals

Cell Adhesion Molecules - analysis

Models, Animal

Mice

Antigens, Neoplasm - analysis

Antigens, CD

Drug Screening Assays, Antitumor

Details

Title: Subtitle: Novel mouse model for carcinoembryonic antigen-based therapy
Creators: Carlos H F Chan - Department of Biochemistry and McGill Cancer Centre, McGill University, Montreal, Quebec, Canada H3G 1Y6
Clifford P Stanners
Resource Type: Journal article
Publication Details: Molecular therapy, Vol.9(6), pp.775-785
DOI: 10.1016/j.ymthe.2004.03.009
PMID: 15194045
NLM abbreviation: Mol Ther
ISSN: 1525-0016
eISSN: 1525-0024
Publisher: United States
Language: English
Date published: 06/2004
Academic Unit: Surgery; Radiation Oncology
Record Identifier: 9984047656202771

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