Carcinoembryonic Antigen Transgenic Mouse Models for Immunotherapy and Development of Cancer Vaccines

Abstract

The goal of cancer therapy remains as the long-term eradication of tumor cells without adverse effects on normal tissue. Conventional approaches utilizing chemotherapy and radiotherapy are limited by both their toxicity and lack of specificity. In recent years, investigators have carried out several studies designed to evaluate whether human tumor-associated antigens (TAAs) can be exploited as targets for immunotherapy, specifically for human cancer vaccine development. A major limitation in immunotherapy studies of human cancer is the general lack of appropriate preclinical models. Clinical studies can be difficult to implement, particularly when a clear understanding of the potential efficacy, limitation, and safety of an immunotherapeutic strategy is not available from relevant animal investigations. However, mice carrying a transgene for a human tumor self-antigen may provide a more acceptable experimental model in which knowledge about immunotherapeutic strategies aiming at the TAA of interest can be enhanced prior to initiating clinical trials. Since the different strategies in experimental immunotherapy of cancer have been directed to activate different immune system components, a variety of transgenic mouse models have been generated expressing either TAA, human leukocyte antigen (HLA), oncogene, or immune effector cell molecules. These models may serve as an excellent platform for the identification of novel targets for immunotherapy as well as to evaluate the efficacy of targeted therapies and will lead to the development of clinical trials for cancer patients. In this unit, a brief overview of the generation and study of different vaccine approaches in carcinoembryonic antigen (CEA) transgenic mouse models and the experimental findings in mouse models that spontaneously develop gastrointestinal tumors and express the CEA transgene is provided.

Opa proteins and CEACAMs: pathways of immune engagement for pathogenicNeisseria

“…The majority of experimental work has therefore been carried out using cell lines that have been transfected to expresss CEACAM proteins. The recent development of transgenic animal models that are able to express human CEACAM should provide a wider perspective in the near future (Bhattacharya-Chatterjee et al, 2008;Gu et al, 2010;Muenzner et al, 2010;Sarantis et al, 2010). (Williams & Barclay, 1988).…”

Estradiol-Treated Female Mice as Surrogate Hosts for Neisseria gonorrhoeae Genital Tract Infections

“…Opa–CEACAM-1 binding causes immunosuppression of T cells and killing of B cells (Sadarangani et al, 2011). CEACAM transgenic mice are available (Eades-Perner et al, 1994; Bhattacharya-Chatterjee et al, 2008) and CEACAM-5 transgenic mice were recently used by Christof Hauck's laboratory to demonstrate a novel role for Opa–CEACAM interactions in preventing detachment of infected epithelial cells via enhancement of integrin-mediated cell to cell adhesion and cellular adhesion to extracellular matix. CEACAM-5 transgenic mice had a higher colonization load than normal mice 1 day after inoculation.…”

TCR Retrogenic Mice as a Model To Map Self-Tolerance Mechanisms to the Cancer Mucosa Antigen GUCY2C

“…Many transgenic mouse lines have been generated but with limitations. There have been several reports of differences in patterns of CEA expression across cell types and mouse strains, with CEA levels higher than the concentration detected in humans by 20-fold in some cases (56), confounding findings of toxicity in these models (57). Although models improve as new technologies evolve, studies of CEA still require models with greater translational potential for the treatment of human disease.…”