B6-hPDL1-V Mice

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Catalog Number: C001420

Genetic Background: C57BL/6NCya

Reproduction: Homozygote x Homozygote


Strain Description

Programmed cell death 1 ligand 1 (PD-L1), also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7H1), is an immune inhibitory receptor ligand. PD-L1 is a type I transmembrane protein with immunoglobulin V-like (IgV) and C-like (IgC) structural domains and is expressed by hematopoietic and non-hematopoietic cells, including T cells, B cells, and various types of tumor cells [1]. PD-L1 can bind to the PD-1 on the surface of CD8+ T cells, inhibiting the activity of CD8+ T cells. This interaction can prevent the immune system from damaging normal tissues, but it can also be used by tumor cells to escape immune surveillance. Monoclonal antibodies that competitively bind to PD-L1 can relieve the immune function inhibition mediated by the binding of PD-1 and PD-L1. This can reactivate CD8+ T cells, triggering the human body's anti-tumor immune response [2]. Therefore, developing of antibody drugs targeting PD-1 and PD-L1 is a hot area in tumor immunotherapy.

This strain is a humanized model of the mouse Pdl1 gene in which the gene sequence encoding the extracellular domain (immunoglobulin V-like, IgV-like) of mouse PD-L1 protein is replaced with the corresponding human PD-L1 gene sequence. B6-hPDL1-V mice can be used for the research of PD-L1 targeted drug development screening, efficacy and safety evaluation, tumor immunotherapy evaluation, and immune system mechanisms [2-4].

 

The gene sequence encoding the extracellular domain (immunoglobulin V-like, IgV-like) of mouse PD-L1 protein is replaced with the corresponding human PD-L1 gene sequence, while the sequence encoding the signal peptide is retained.

Figure 1. Schematic representation of the gene editing strategy for generating B6-hPDL1-V mice.

● Development and screening of PD-L1-targeted drugs;

● Efficacy and safety evaluation of PD-L1-targeted drugs;

● Evaluation of tumor immunotherapy; [5];

● Research on the immune system and tumor immune escape mechanisms.

1. Detection of species-specific PD-L1 protein expression

Figure 2. Expression of PD-L1 protein in peripheral blood (PB) and spleen of wild-type (C57BL/6N) and B6-hPDL1-V mice. Flow cytometry analysis was used to detect the expression of human and mouse CD274 in homozygous B6-hPDL1-V mice and C57BL/6N mice using species-specific PD-L1 (CD274) antibodies. The results showed that human CD274 protein (hCD274) was expressed in both the peripheral blood and spleen of homozygous B6-hPDL1-V mice, and the proportion of cells expressing hCD274 was consistent with the proportion of cells expressing mouse CD274 (mCD274) in wild-type mice.

Reference

[1] Kornepati AVR, Vadlamudi RK, Curiel TJ. Programmed death ligand 1 signals in cancer cells. Nat Rev Cancer. 2022 Mar;22(3):174-189.

[2] Escors D, Gato-Cañas M, Zuazo M, Arasanz H, García-Granda MJ, Vera R, Kochan G. The intracellular signalosome of PD-L1 in cancer cells. Signal Transduct Target Ther. 2018 Sep 28;3:26.

[3] Huang CY, Wang Y, Luo GY, Han F, Li YQ, Zhou ZG, Xu GL. Relationship Between PD-L1 Expression and CD8+ T-cell Immune Responses in Hepatocellular Carcinoma. J Immunother. 2017 Nov/Dec;40(9):323-333.

[4] Zhang C, Wu S, Xue X, Li M, Qin X, Li W, Han W, Zhang Y. Anti-tumor immunotherapy by blockade of the PD-1/PD-L1 pathway with recombinant human PD-1-IgV. Cytotherapy. 2008;10(7):711-9.