Immune Checkpoint Mouse Models
Applied StemCell’s off-shelf mouse catalog offers >100 humanized immune checkpoint mouse models, with single, double, and triple humanized gene models.
- Knock-in of humanized counterparts of immune checkpoint gene into the endogenous locus.
- Proprietary human transgene knock-in strategy to enable screening of many different antibodies and immuno-therapy compounds.
- In vivo and in vitro validated for physiological expression of human version of the genes (in-house and through collaborators).
- Fully functional murine immune system
- The humanized immune checkpoint mice have been generated in the most widely used C57BL/6J background used in immunology and oncology studies.
- Ideal for immunology and antibody/ immuno-oncology therapy efficacy studies and drug discovery research.
Validation Data for Humanized PD-L1 Mouse
Strain Name: C57BL/6J-Cd274em1(hPD-L1)Asc Strain Background: C57BL/6J
Programmed cell death 1 ligand (PD-L1), also known as cluster of differentiation 274(CD274) or B7 homolog 1 (B7H1), is a 40kDa transmembrane protein encoded by the gene CD274 in human. The binding of PD-L1 to the PD-1 receptors expressed on the surface of activated T cells transmits a negative regulatory signal. While under normal circumstances the PD-L1 pathway acts as a type of "off switch" that helps keep the T cells from attacking other cells, the high expression level of PD-L1 in the tumor microenvironment inhibits the function of tumor-infiltrating T cells, thereby allowing tumors cells to escape immune surveillance.
Figure 1. Generation strategy of humanized PD-L1 mice. The full-length protein coding sequence for human PD-L1 was placed immediately downstream of the start codon of the mouse endogenous Pd-l1 gene, followed by a poly(A) site, so that the expression of endogenous Pd-l1 in the mouse was replaced by the expression of fully humanized PD-L1 protein. This mouse model was generated in the C57BL/6J genetic background.
Figure 2. hPD-L1 expression in spleen T cells after stimulation. Flow cytometry analysis of spleen lymphocytes collected from homozygous humanized PD-L1 mice and wild-type C57BL/6J mice. The results showed that the expression of human PD-L1 can be detected in both T cells and B cells collected from the spleen of homozygous humanized PD-L1 mice. (Data provided by collaborators).
Figure 3. In vivo validation of anti-tumor efficacy in a MC38 tumor-bearing model of humanized PD-L1 mice. Mouse colon cancer cells MC38 engineered to express human PD-L1 were implanted subcutaneously into homozygous, humanized PD-L1 mice. The mice were randomly assigned into two groups when the tumor volume reached 100 mm3, with one group receiving human IgG as a control and the other receiving a human-specific, PD-L1 antibody (n=5). The human PD-L1 blocking antibody significantly inhibited tumor growth in the homozygous humanized mice (Left) without affecting overall body weight (Right), suggesting that the humanized PD-L1 mice represent an ideal model for evaluating the efficacy of therapeutic antibodies targeting human PD-L1. (TGI: tumor growth inhibition; 67%; p < 0.001), demonstrating that the humanized PD-L1 mice are a good in vivo model for validating the efficacy of antibodies targeting human PD-L1.
| Double Humanized
|CTLA4||CD81||PD-1 & GITR||PD-1 & PD-L1 & OX40|
|CTLA4||CEACAM1||PD-L1 & GITR||PD-1 & PD-L1 & LAG3|
|PD-1||CSF1||LAG3 & CTLA4||PD-1 & PD-L1 & PDCD1LG2|
|PD-L1||CSF2||OX40 & CTLA4||PD-1 & PD-L1 & IDO1|
|PD-L1||CSF3||PD-1 & CTLA4||PD-1 & TIGIT & TIM3|
|GITR||CXCR2||PD-1 & LAG3||SIRPA & CD47 & PD-1|
|OX40||Dpp4||PD-L1 & CTLA4|
|OX40L||ENPP1||LAG3 & TIM3|
|VISTA||FcRn||CTLA4 & ICOS|
|CD3E||GITR||PD-1 & CD27|
|BTLA||HGF||PD-1 & CD47|
|CD276||ICOS||PD-1 & NT5E|
|CD27||ICOS||PD-L1 & CD27|
|CD38||ICOSL||PD-L1 & CD47|
|CSF1R||IL17F||TIM3 & CEACAM1|
|IL6||IL17RA||ICOS & ICOSL|
|Nt5e||IL1B||PD-1 & TIGIT|
|TNFSF15||IL23A||PD-L1 & TIGIT|
|VISTA||IL2||CD19 & CD3E|
|4-1BBL||IL2RA||CTLA4 & 4-1BB|
|CD4||IL3||IL3 & CSF2|
|CD80||IL3||IL6 & IL6R|
|CD86||IL4RA||PD-1 & 4-1BB|
|IDO1||II5||PD-1 & CD3e|
|IL17A||IL5RA||PD-1 & CD40|
|IL6R||IL7||PD-1 & OX40|
|OX40||IL9||PD-1 & PD-L1|
|PSGL-1||KDR||PD-1 & SEMA4D|
|TNFRSF25||KLRK1||PD-1 & SIRPA|
|VTCN1||LAG3||PD-1 & TIM3|
|4-1BB||PCSK9||PD-1 & TLR9|
|APOE2||PDCD1LG2||PD-L1 & 4-1BB|
|APOE3||PDCD1LG2||PD-L1 & CD40|
|APOE4||PVR||PD-L1 & LAG3|
|BTLA||SEMA4D||PD-L1 & OX40|
|CCR2||SIGLEC15||PD-L1 & SEMA4D|
|CCR4||SIRPA||PD-L1 & TIM3|
|CCR8||SIRPA||SIRPA & CD47|
|CD160||SLAMF7||TLR9 & OX40|