General Information

Development

CTLA4, also known as CD152, is an immune checkpoint protein receptor expressed on activated regulatory T cells that down-regulates immune responses. In tumor tissues, it acts as an “off” switch when bound to CD80 or CD86 on the surface of antigen-presenting cells, leading to the escape of tumor cells. The humanized CTLA4 antibody can be used in efficacy or drug screening assays.

We used a CRISPR-Cas9-assisted method to replace the extracellular region of mouse CTLA4 with a human sequence. This allows recognition and biological function in CTLA4 humanized mice when using human CTLA4 antibody inhibitors, which can be used in relevant pharmacodynamic or drug screening experiments.

Fig 1. Construction strategy of hCTLA4 mice

Phenotype

1. Splenic Lymphocyte hCTLA4 Detection

Fig 2. hCTLA4 is expressed in splenic lymphocytes of hCTLA4 mice

Application cases

1. Constructing colon cancer model and therapeutic efficacy

Fig 3. hCTLA4 mice transplanted with MC38 and Yervoy efficacy

hCTLA4 mice were subcutaneously inoculated with mouse MC38 colon cancer cell line. When the tumors grew to approximately 100 mm³, the animals were randomly divided into two groups (n=6, 3 male and 3 female), with the control group receiving a physiological saline injection and the experimental group receiving Yervoy. The results showed that Yervoy exhibited a significant tumor-inhibiting effect on the humanized CTLA4 mice.

hCTLA4 Mice Applications

1. CTLA4-related pharmacodynamic or drug screening experiments

2. Research on CTLA4-targeted immunomodulation for anti-tumor, anti-infection, anti-autoimmune diseases and organ transplantation survival

Reference

1. Dariavach P, Mattéi MG, Golstein P, et al. Human Ig superfamily CTLA-4 gene: chromosomal localization and identity of protein sequence between murine and human CTLA-4 cytoplasmic domains. Eur. J. Immunol. 1988, 18(12): 1901–1905.