Figure 6.
JNJ-64407564 can inhibit and regress tumors in murine models of MM. (A) JNJ-64407564 inhibits H929 tumor growth in a prophylactic xenograft model. NSG mice were injected IV with 1 × 107 human PBMCs, and after 7 days, each mouse received SC injection of 5 × 106 H929 cells in the right flank followed by IV administration of PBS (black circles) or JNJ-64407564 antibody at 0.1 µg (0.005 mg/kg, green downward triangle), 1 µg (0.05 mg/kg, red upward triangle), or 10 µg (0.5 mg/kg, blue square) per animal on days 0, 3, 5, 7, and 10. By day 19, the mean tumor volume of the PBS-treated control group (n = 6) had exceeded 600 mm3, and the mice were terminated. (B) JNJ-64407564 causes tumor regression in MM.1S MM xenograft model. Each mouse received 1 × 107 MM.1S cells in PBS in a total volume of 0.2 mL. Cells were implanted SC in the right flank using a 1-cm3 syringe and a 26-gauge needle. The day of tumor cell implantation was designated as day 0. On day 7 after tumor cell implant, animals were randomized with a tumor volume of ∼75 mm3 and received IV injection of 1 × 107 human PBMCs. Treatments were initiated on day 15, with each mouse receiving IV administration of PBS (black square) or JNJ-64407564 at 0.1 µg (0.005 mg/kg, blue circle), 1 µg (0.05 mg/kg, green upward triangle), 10 µg (0.5 mg/kg, red downward triangle), or 50 µg (2.5 mg/kg, orange diamond). Null bispecific antibody controls, GPRC5DxNull (dark green open square) and NullxCD3 (purple open circle), were each dosed at 10 µg per mouse. Treatments were administered for a total of 7 doses on days 15, 18, 22, 24, 29, 32, and 36 (indicated as “x” on the x-axis). Tumor measurements were taken up to day 36, when 80% to 100% of mice remained on study for each group. SEM, standard error of the mean.