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NCG-HLA-A2.1

 

Strain Name: NOD/ShiLtJGpt -Prkdc em26Cd52Il2rg em26Cd22 H2-K emCin(HLA-A2.1) /Gpt

Strain Type: Knock-in

Strain ID: T003278

Background: NOD/ShiLtJGpt

 

Application

1. Vaccine research

2. Hematopoietic Stem Cell Transplantation

3. Establish the humanized immune system

4. Immune system research

 

Description

HLA-A, one of three major types of human MHC class I cell surface receptors, is a group of human leukocyte antigens (HLA) that are coded by the HLA-A locus. MHC I consists of an alpha chain and a beta chain (encoded by the B2M gene). The alpha chain comprises the variable regions α1, α2 responsible for antigen binding and the constant α3, transmembrane and intracellular regions for CD8 interaction and signal transduction respectively.

The NCG-HLA 2.1 mouse model was developed using gene editing technology based on the severe immune deficient model NCG, the α1, α2, α3 domain is replaced by their human derived counterparts, while the murine transmembrane and intracellular regions are retained. Studies have confirmed that the interaction between α3 and CD8 is species-specific, thus the human α3 domain would facilitate the reconstituted CD8+ T cells development and correct HLA-A2.1 restricted CTL recognition. NCG-HLA-A2.1 is an ideal model for hematopoietic reconstitution and immune oncology research.

 

Strategy

Strategy of humanized MHC I mouse

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Data support

MHCI expression level detection

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Detection of MHCI expression on NCG-HLA-A2.1 mice. Only H2K in mouse spleen cells was detected in WT mice, and hHLA could be detected in the humanized homozygous mouse.

T/B/NK cell ratio assay

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Detection of T/B/NK cells proportion on NCG-HLA-A2.1 mice. There were almost no CD3+T(< 0.05%), CD19+B (< 0.1%) ,NK(<0.1%) cells and CD4+/CD8+T cells in peripheral blood of HLA humanized mice, and the results were the same as in the control group.

In vivo efficacy test

Tumor efficacy of Ab-1 antibody was tested after subcutaneous inoculation of Raji-PBMC mixed cells in NCG-HLA-A2.1 mouse model

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In vivo efficacy test with NCG-HLA-A2.1 (Data from third party)

The logarithmic growth phase lymphoma Raji and HLA match PBMC cells were inoculated subcutaneously into 6-8 weeks old NCG-HLA-A2.1and NCG mice. Randomly divide the animals into Vehicle (NCG-WT), Vehicle (NCG-HLA), Ab-1 (NCG-WT) treated group (n=7) and Ab-1 (NCG-HLA) treated group (n=7) when the mean tumor volume reach 70mm3. The animals are administered twice a week with vehicle or antibody for a total of 6 doses. The results demonstrate that NCG-HLA-A2.1 is an ideal model for in vivo evaluation of immune modulatory anti-tumor drugs.


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Time:2020-01-14

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