B-hPD-1/hPD-L1/hCD94/hNKG2A mice_Biocytogen Pharmaceuticals (Beijing) Co., Ltd._Biocytogen,drug development,antibody discovery

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動物・細胞モデル

Humanized Mouse Models

Immune-checkpoint Humanized Mice

Text

B-hPD-1/hPD-L1/hCD94/hNKG2A mice

Strain Name

C57BL/6-Pdcd1^{tm1(PDCD1)Bcgen}Cd274^{tm1(CD274)Bcgen}Klrd1^{tm1(KLRD1)Bcgen}Klrc1^{tm1(KLRC1)Bcgen}/Bcgen

Common Name

B-hPD-1/hPD-L1/hCD94/hNKG2A mice

Background

C57BL/6

Catalog number

111848

Related Genes

CD94,KLRD1, NKG2A, KLRC1, CD159a；

PD-1 (Programmed death-1) ;

CD274 (CD274 antigen)

Protein expression analysis of PD-1/PD-L1 in T cell

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Strain specific PD1 and PD-L1 expression analysis in homozygous B-hPD-1/hPD-L1/hCD94/hNKG2A mice by flow cytometry. Splenocytes were collected from wild type mice(+/+) and homozygous B-hPD-1/hPD-L1/hCD94/hNKG2A mice (H/H; H/H; H/H; H/H) stimulated with anti-CD3ε in vivo , and analyzed by flow cytometry with species-specific anti-PD-1 and anti-PD-L1 antibodies. Mouse PD-1 and PD-L1 were exclusively detectable in wild type mice. Human PD-1 and PD-L1 were exclusively detectable in homozygous B-hPD-1/hPD-L1/hCD94/hNKG2A mice but not in wild type mice.

Protein expression analysis of NKG2A/CD94 in NK cell

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Strain specific CD94 and NKG2A expression analysis in homozygous B-hPD-1/hPD-L1/hCD94/hNKG2A mice by flow cytometry. Splenocytes were collected from wild type mice(+/+) and homozygous B-hPD-1/hPD-L1/hCD94/hNKG2A mice (H/H; H/H; H/H; H/H), and analyzed by flow cytometry with species-specific CD94 or NKG2A antibody. Mouse CD94 and NKG2A were detectable in wild type mice. Human CD94 and NKG2A were exclusively detectable in homozygous B-hPD-1/hPD-L1/hCD94/hNKG2A mice but not wild type mice. (Monalizumab wasused to detect the human NKG2A protein expression)

Protein expression analysis of NKG2A/CD94 in activated CD8+ T cells

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Strain specific CD94 and NKG2A expression analysis in homozygous B-hPD-1/hPD-L1/hCD94/hNKG2A mice by flow cytometry. Splenocytes were collected from wild type mice and homozygous B-hPD-1/hPD-L1/hCD94/hNKG2A mice (H/H; H/H; H/H; H/H), and analyzed by flow cytometry with species-specific CD94 or NKG2A antibody. Spleen cells were stimulated for the 5 days coated with 5 μg/ml anti-TCRβ mAb before analysis. Mouse CD94 and NKG2A were detectable in wild type mice. Human CD94 and NKG2A were exclusively detectable in homozygous B-hPD-1/hPD-L1/hCD94/hNKG2A mice but not wild type mice. (Monalizumab was used to detect the human NKG2A expression)

Combination therapy of anti-human PD-L1 antibody and anti-human NKG2A antibody

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Antitumor activity of anti-human NKG2A antibodies and anti-human PD-L1 antibodies in B-hPD-1/hPDL1/hCD94/hNKG2A mice. (A) Anti-human NKG2A antibodies (in house) combined with anti-human PD-L1 antibodies (in house) inhibited B-hHLA-E plus/hPD-L1 MC38 tumor growth in B-hPD-1/hPDL1/hCD94/hNKG2A mice. Murine colon cancer B-hHLA-E plus/hPD-L1 MC38 cells were subcutaneously implanted into homozygous B-hPD-1/hPDL1/hCD94/hNKG2A (female, 7-8-week-old, n=6). Mice were grouped when tumor volume reached approximately 100 mm³, at which time they were treated with anti-hNKG2A Ab1 and anti-hPD-L1 Ab2. (B) Body weight changes during treatment. As shown in panel A, combination of hPD-L1 and hNKG2A antibodies were more efficacious in controlling tumor growth in B-hPD-1/hPDL1/hCD94/hNKG2A mice. B-hPD-1/hPDL1/hCD94/hNKG2A mice is a powerful preclinical model for in vivo evaluation of anti-human PD-L1 and NKG2A antibodies. Values are expressed as mean ± SEM.