Cynomolgus and Human B Cell Activation by CEA×CD40 Bispecific Antibody

Example 20

Materials and Methods

B cell activation of the cynoCEA×CD40 RUBY™ (AC_05355) on cynomolgus and human B cells in the presence of CEA transfected cells (macaque CEA, NP_001040590.1). Primary cynomolgus B cells were cultured with titrated antibodies in the presence CEA expressed on CHO cells. After 2 days, expression of CD86 on B cells was analyzed by FACS.

The cynoCEA×CD40 bispecific antibody (AC_05355) was administered once weekly via intravenous infusion for 2 weeks to cynomolgus monkeys at two different dose levels (10 mg/kg and 37.5 mg/kg). One female and one male were evaluated at each dose level.

Results

FIG. 29 shows that CEA×CD40 bsAbs in the RUBY™ format (AC_05355) induce upregulation of CD86 on cynomolgus and human B cells to a similar degree. The CEA-conditional activation of CD40 on cynomolgus B cells and human B cells is similar to what is observed with the human CEA×CD40 bsAb in RUBY™ (AC_05355) used for the in vitro assays. The cynoCEA×CD40 bsAb binds with similar affinity to human and cynomolgus monkey CEA (hCEA vs cCEA, right panel).

FIG. 29 also shows that in cynomolgus monkeys there were no findings associated with cyoCEA×CD40 bsAb (AC_05355) at the evaluated dose levels.