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