CTLA4 Humanized Mice
CTLA4 humanized mice express human cytotoxic T lymphocyte associated protein 4, enabling preclinical testing of anti CTLA4 antibodies including ipilimumab in immunocompetent mice.
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CTLA4 Biology and Therapeutic Relevance
Cytotoxic T lymphocyte associated protein 4 (CTLA4, CD152) is a critical immune checkpoint that regulates T cell activation. Blocking CTLA4 with antibodies such as ipilimumab enhances antitumor immunity and was the first checkpoint inhibitor approved for cancer treatment.
Key CTLA4 Biology
- CTLA4 is an inhibitory receptor expressed on activated T cells and constitutively on regulatory T cells
- CTLA4 competes with the costimulatory receptor CD28 for binding to B7 ligands (CD80 and CD86)
- CTLA4 engagement suppresses T cell activation
- Blocking CTLA4 with antibodies enhances T cell activation and antitumor immunity
Species Specificity Challenge
Therapeutic anti CTLA4 antibodies are designed to bind human CTLA4 and typically do not cross react with mouse CTLA4. CTLA4 humanized mice solve this problem by expressing human CTLA4, enabling preclinical evaluation of human specific antibodies.
Applications
Anti CTLA4 Antibody Development
CTLA4 humanized mice enable preclinical efficacy testing of anti CTLA4 antibodies including ipilimumab biosimilars and novel antibodies with modified Fc regions.
Combination Immunotherapy
Double humanized mice expressing both human CTLA4 and human PD1 enable preclinical testing of combination checkpoint blockade strategies.
Toxicity and Safety Studies
CTLA4 humanized mice support safety assessment of anti CTLA4 antibodies. Immune related adverse events can be modeled and mitigation strategies evaluated.
Mechanism of Action Studies
Humanized mice enable study of antibody effects on T cell activation, regulatory T cell function, and tumor immune infiltration.
CTLA4 Humanization Strategy
Extracellular Domain Humanization
Humanizes the extracellular domain where therapeutic antibodies bind, while retaining mouse transmembrane and intracellular domains. Maintains normal CTLA4 signaling while enabling human antibody binding.
Complete Gene Replacement
Complete replacement of mouse CTLA4 with human CTLA4 provides a fully humanized target but may affect T cell function if human CTLA4 interacts differently with mouse signaling partners.
Tumor Model Compatibility
CTLA4 humanized mice are generated on the C57BL/6 background, providing compatibility with established syngeneic tumor models for checkpoint inhibitor efficacy studies.
MC38
Colon carcinoma
B16
Melanoma
E0771
Breast carcinoma
Lewis Lung
Lung carcinoma
Available Designs
- Single immune checkpoint models: CTLA4 humanized mice as standalone models
- Double immune checkpoint models: CTLA4 humanized combined with PD1 humanized
- Triple and multi checkpoint models: CTLA4 combined with multiple checkpoint humanizations
What Researchers Say
“iTL generated a conventional knockout mouse for my lab. The entire process was smooth and the quality of service provided by the iTL team and our project manager was exceptional. Several other researchers in my Center are creating mice with iTL and all of us have been extremely satisfied. I strongly recommend iTL for generation of your next mouse model!!!”
— Terry K. Means, PhD
Sanofi
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