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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Animal models of tumor immunity, immunotherapy and cancer vaccines
1Department of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle Baltimore, MD 21250, USA. srosenbe@umbc.edu
Abstract:
Reliable animal models are critical for evaluating immunotherapies and for defining tumor immunology paradigms. Tumor immunologists are moving away from traditional transplantation tumor systems because they do not adequately model human malignancies. Transgenic mouse models in which tumors arise spontaneously have been developed for most cancers. The models use one of three technologies: tissue-specific promoters to drive expression of SV40 large T antigen or tissue-specific oncogenes; deletion of tumor suppressor genes by gene targeting; or, conditional deletion of tumor suppressor genes or activation of oncogenes via Cre-lox technology. Knockin mice expressing human tumor antigens and gene-targeted mice with deletions for immunologically relevant molecules have been integral to advancing knowledge of the tumor-host relationship. Although animal models are becoming more sophisticated, additional improvements are needed so that more realistic models can be developed.
Insights
Developing advanced animal models is crucial for cancer immunotherapy research. Spontaneous tumor models in transgenic mice offer more realistic human cancer insights than traditional systems.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Traditional tumor transplantation models inadequately represent human malignancies.
- Advancements in tumor immunology necessitate more accurate preclinical models.
- Spontaneously arising tumors in transgenic mice offer improved human cancer relevance.
Purpose of the Study:
- To review the development and application of transgenic mouse models for cancer immunotherapy research.
- To highlight the technologies utilized in creating sophisticated animal models for tumor immunology.
- To discuss the importance of these models in understanding the tumor-host relationship.
Main Methods:
- Utilizing tissue-specific promoters to drive oncogene expression (e.g., SV40 large T antigen).
- Employing gene targeting for the deletion of tumor suppressor genes.
- Implementing Cre-lox technology for conditional gene manipulation (deletion or activation).
- Developing knockin mice expressing human tumor antigens and gene-targeted models with specific molecular deletions.
Main Results:
- Transgenic mouse models now exist for most cancer types, enabling spontaneous tumor development.
- These models facilitate the study of tumor immunology and the tumor-host interaction.
- Knockin and gene-targeted mice have significantly advanced understanding of tumor immunology.
Conclusions:
- Sophisticated transgenic mouse models are essential for evaluating cancer immunotherapies.
- Current models provide superior representation of human cancers compared to older systems.
- Continued refinement of animal models is needed for even greater realism in preclinical research.
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