Preclinical CD3-based Mouse Models for Evaluation of Bi-specific T-cell Engager Antibodies
SUMMARY
mRNA and protein expression analysis: Human Cd3e mRNA was exclusively detected B-hCD3E mice and human Cd3e, Cd3d, Cd3g mRNAs were exclusively detected in B-hCD3EDG mice. Human CD3E protein expression was confirmed by flow cytometry in B-hCD3E and B-hCD3EDG mice.
Immune cell analysis: Humanized B-hCD3E and B-hCD3EDG mice demonstrated normal immune cell development compared with wild-type C57BL/6 mice.
T-cell activation analysis: When stimulated with an anti-CD3 antibody in vitro, wildtype C57BL/6 and humanized CD3-based mice displayed similar levels of T-cell activation and cytokine production.
In vivo efficacy evaluation: Bispecific anti-human CD3/CD19 antibody blinatumomab dose-dependently inhibited MC38- hCD19 tumor growth in B-hCD3E mice, and bispecific anti-human CD3/BCMA antibody dose-dependently inhibited MC38-hBCMA tumor growth in B-hCD3EDG mice.
Used in the study: B-hCD3E mice, B-hCD3EDG mice