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Catalog Models

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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Ready to discuss humanized mice for your immunotherapy research? Our scientific team provides complimentary consultation to help you select the optimal checkpoint model design.

Frequently Asked Questions

Full humanization replaces the entire mouse CTLA4 gene with human CTLA4 sequence. ECD only humanization replaces only the extracellular domain while retaining mouse transmembrane and cytoplasmic domains. Full humanization is preferred for antibody testing, while ECD only may preserve some mouse signaling functions.

Yes. CTLA4 humanization can be combined with PD1, PDL1, LAG3, TIM3, or other checkpoint humanizations to create double, triple, or multi checkpoint models. These models enable testing of combination checkpoint blockade therapies in immunocompetent animals with human targets.

Yes. CTLA4 humanized mice can be combined with syngeneic tumor cell lines to create systems where both tumor and immune compartments express human targets. This enables evaluation of checkpoint blockade in immunocompetent animals with intact tumor immunity.

CTLA4 humanized mice on C57BL/6 background are compatible with MC38 (colon carcinoma), B16 (melanoma), E0771 (breast carcinoma), and Lewis lung carcinoma. These syngeneic models enable evaluation of anti CTLA4 antibody efficacy in various tumor contexts.