Basic Information

Strain Name
C57BL/6-Pdcd1tm1(PDCD1) Tnfrsf18tm1(TNFRSF18)/Bcgen
Stock Number
120528
Common Name
B-hPD-1/hGITR mice
Source/Investigator
Bcgen (Beijing Biocytogen Co., Ltd)
Related Genes
Pd-1 (Programmed death-1);Tnfrsf18 (tumor necrosis factor receptor superfamily, member 18)
Species
C57BL/6
Appearance
Black
Genotypes
Homozygous
NCBI Gene ID

Details

Protein Expression Analysis

Splenocytes from both wild type (WT) C57BL/6 and homozygous B-PD-1/hGITR mice were analyzed by flow cytometry. Mouse PD-1 + T cells were only detectable in the WT C57BL/6 mice, while human PD-1 + T cells were only detectable in the homozygous B-hPD-1/hGITR mice.

Splenocytes from both wild type (WT) C57BL/6 and homozygous B-PD-1/hGITR mice were analyzed by flow cytometry. Mouse GITR + T cells were only detectable in the WT C57BL/6 mice, while human GITR + T cells were only detectable in the homozygous B-hPD-1/hGITR mice.

Analysis of leukocytes cell subpopulation in B-hPD-1/hGITRmice

Analysis of leukocytes subpopulation in spleen .Splenocytes were isolated from C57BL/6 and B-hPD-1/hGITR mice (n=3). The proportion of leukocytes subpopulation was tested by flow cytometry. As a result, the expression profile of leukocytes subpopulation in homozygous B-hPD-1/hGITR mice is similar to that in the C57BL/6 mice, indicating that differentiation of T, B, NK, Monocyte, DC and macrophage cells are not affected by the humanization of hPD-1/hGITR.

routine test

Blood Routine Test. Blood from the C57BL/6 and B-hPD-1/hGITR mice (n=3) was collected and analyzed by blood routine test. As a result, there is no significant differences between the C57BL/6 and B-hPD-1/hGITR mice.

Blood Biochemical test

Blood Biochemical Test. Serum AST/ALT levels of C57BL/6 and B-hPD-1/hGITR mice were tested (n=3). Results indicate that there is no significant differences between the C57BL/6 and B-hPD-1/hGITR mice.

Combination Therapy of PD-1 Ab and GITR Ab Efficacy Evaluation

Antitumor activity of anti-GITR antibody INCAGN01876 combined with anti-hPD-1 antibody pembrolizumab in B-hPD-1/hGITR mice. (A) Anti-hGITR antibody INCAGN01876 (in house) combined with anti-hPD-1 antibodies pembrolizumab inhibited MC38-hPD-L1 tumor growth in B-hPD-1/hGITR mice. Murine colon cancer MC38-hPD-L1 cells (5×105) were subcutaneously implanted into homozygous B-hPD-1/hGITR mice (female, 7 week-old, n=5). Mice were grouped when tumor volume reached approximately 100-150 mm3, at which time they were treated with antibody INCAGN01876 combined with anti-hPD-1 antibody pembrolizumab with doses and schedules indicated in panel (B) Body weight changes during treatment. As shown in panel A, combination of anti-hGITR and anti-hPD-1 antibody shows more inhibitory effects than individual groups, demonstrating that the B-hPD-1/hGITR mice provide a powerful preclinical model for in vivo evaluating combination therapy efficacy of hGITR antibodies and hPD-1 antibodies . Values are expressed as mean ± SEM.

Combination Therapy of PD-1 Ab and GITR Ab Efficacy Evaluation

Antitumor activity of anti-GITR antibody BMS-28F3 combined with anti-hPD-1 antibody pembrolizumab in B-hPD-1/hGITR mice. (A) Anti-hGITR antibody BMS-28F3 (in house) combined with anti-hPD-1 antibodies pembrolizumab inhibited MC38-hPD-L1 tumor growth in B-hPD-1/hGITR mice. Murine colon cancer MC38-hPD-L1 cells (5×105) were subcutaneously implanted into homozygous B-hPD-1/hGITR mice (female, 7 week-old, n=5). Mice were grouped when tumor volume reached approximately 100-150 mm3, at which time they were treated with antibody BMS-28F3 (in house) combined with anti-hPD-1 antibody pembrolizumab with doses and schedules indicated in panel (B) Body weight changes during treatment. As shown in panel A, combination of anti-hGITR and anti-hPD-1 antibody shows more inhibitory effects than individual groups, demonstrating that the B-hPD-1/hGITR mice provide a powerful preclinical model for in vivo evaluating combination therapy efficacy of hGITR antibodies and hPD-1 antibodies . Values are expressed as mean ± SEM.

References

  1. Nat Commun.2017 Feb 6;8:14369. doi: 10.1038/ncomms14369.
  2. EMBO J.1992 Nov;11(11):3887-95.
  3. ONCOIMMUNOLOGY. 2017, VOL. 6, NO. 3, e1280645 (14 pages). doi: 10.1080/2162402X.2017.1280645