1. B-hCD40マウスで抗ヒトCD40抗体のin vivo効果と安全性の評価
Anti-human CD40 antibodies were administered i.p. in homozygous B-hCD40 mice on days indicated by red arrows (n=5). No significant difference in average body weight was detected over the course of the treatment.
Abbreviation Stand for Stand for Stand for WBC White Blood Cell Count MCV Mean Corpuscular Volume NE＃ Neutrophil Count MCH Mean Corpuscular Hemoglobin LY＃ Lymphocyte Count MCHC Mean Corpuscular Hemoglobin Concentration MO＃ Monocyte Count MPV Mean Platelet Volume RBC Red Blood Cell Count PLT Platelet Count Hb Hemoglobin RDW Red Cell Distribution Width HCT Hematocrit ALT Alanine transaminase High level indicates liver injured AST Aspartate transaminase High level indicates liver damage CHOL Cholesterol High level indicates high blood liquid CR Creatinine High level indicates low glomerular filtration GLU Glucose Hyperglycemia or hypoglycemia TRIG Triacylglycerol High level indicates high blood lipid UREA Urea High level indicates kidney damage, liver disease, diabetes or infection
The blood chemistry was tested with anti-human CD40 antibodies in B-hCD40 mice two days after the termination of efficacy evaluation experiment.
Cytokine profiles in anti-human CD40 antibody treated MC38-bearing B-hCD40 mice. Cytokines were measured by LEGENDplexTM (Biolegend). Anti-human CD40 Ab4 and Ab5 showed different cytokine profiles. Anti-human CD40 Ab4 treatment led to significant increase several cytokines including IFN-γ, MCP-1, and IL-27. Anti-human CD40 Ab5 resulted in significant increase of IL-10. Both antibodies modestly elevated TNF-α.
Flow cytometry was performed to examine immune cell profiles after anti-human CD40 antibody treatment in B-hCD40 mice. The results indicated that CD40 Ab4 treatment resulted in a significant increase in the percentage of activated CD4 and CD8 T cells and B cells.
Anti-human CD40 antibodies were administered i.p. in homozygous B-hCD40 mice After 48h, abdominal cells and splenocytes were collected and analyzed for expression of activation markers by flow cytometry. Selcrelumab led to significant elevation of activation markers in both spleen and abdomen.
Effect of an anti-human CD40 antibody in CBC test in B-hPD-L1/hCD40 mice, where the extracellular domains of both hPD-L1 and hCD40 replace their respective murine counterpart via genomic knock-in. Antibody treatment 6 days after the initial dose led to decrease of MCV, PLT and LY# and increase of NE#, MPV and RDW.
Body weight profile over the course of after antibody administration. No persistent body weight changes were observed.
AST of B-hPD-1/hCD40 mice treated with higher doses increased significantly compared to vehicle control group. Microscopic changes were observed in B-hPD-1/hCD40 mice from the anti-hCD40 antibody treated group of 30mg/kg.
Elevated infiltration of mixed inflammation cells in the interstitium as shown by H&E staining of liver, liung, pancreas, and intestine.
1. B-hCD47/hSIRPAマウスで抗ヒトCD47抗体のin vivo薬効及び毒性の評価
Indication of hematological toxicity of Anti-hCD47 antibodies administered i.p. in homozygous B-hCD47/hSIRPA mice. Blood were collected two days after the treatment. Significant decrease of red blood cell counts (RBC), hematocrit (HCT), were observed upon anti-human CD47 treatment. Monocyte counts were decreased. Anti-human CD47 Ab2 also led to decrease of platelet count.
Abbreviation Stand for Stand for Stand for WBC White Blood Cell Count MCV Mean Corpuscular Volume NE＃ Neutrophil Count MCH Mean Corpuscular Hemoglobin LY＃ Lymphocyte Count MCHC Mean Corpuscular Hemoglobin Concentration MO＃ Monocyte Count MPV Mean Platelet Volume RBC Red Blood Cell Count PLT Platelet Count Hb Hemoglobin RDW Red Cell Distribution Width HCT Hematocrit
Anti-hCD47 antibodies were i.p. injected into homozygous hSIRPA/hCD47 mice. Blood were collected two days after the treatment and analyzed by Blood Routine Test.