NeuroMab™ Anti-CXCR4 BBB Shuttle Antibody(NRZP-1022-ZP3797)

Figure 8G shows the in vivo tumor growth inhibition of various CXCR4+ multiple myeloma cell xenografts by MDX-1338 (BMS-936564).

Panel G, Tumor growth inhibition of MM.1S cell xenografts by MDX-1338 alone or in combination with lenalidomide.

Figure 1A shows the in vivo tumor growth inhibition of various CXCR4+ multiple myeloma cell xenografts by MDX-1338 (BMS-936564).

Panel A, Tumor growth inhibition of OMP-2 cell xenografts by MDX-1338 alone or in combination with bortezomib

Figure 1B shows the in vivo tumor growth inhibition of various CXCR4+ multiple myeloma cell xenografts by MDX-1338 (BMS-936564).

Panel B, Tumor growth inhibition of OPM-2 cell xenografts by MDX-1338 alone or in combination with lenalidomide.

Figure 3 shows that the induction of apoptosis by MDX-1338 (BMS-936564) is CXCR4 specific. MDX-1338 or isotype control was added to R1610 parental cells and stained with Annexin V-FITC and PI. The percentage of cells positive for Annexin V only or double positive for both Annexin V and PI is indicated.

Figure 4 shows inhibition of Ramos cell proliferation by MDX-1338 (BMS-936564), compared to no inhibition by anti-CXCL12.

Figure 5 shows the inhibition of CXCL12-induced migration of CXCR4+ cells by anti-CXCR4 antibody MDX-1338 (BMS-936564) or anti-CXCL12 antibody. Migration assays were performed with CEM cells in the presence of 1.25 nM and 0.05 nM CXCL12, respectively. The number of labeled cells that had migrated to the lower compartment was measured on a Fusion (PerkinElmer) plate reader. Each point represents n=3.

Figure 6A shows inhibition of CXCL12-induced calcium flux in CXCR4+ cells by anti-CXCR4 antibody MDX-1338 (BMS-936564) or anti-CXCL12 antibody. Calcium flux assays were performed by incubating Ramos cells (Figure 8A) or CEM cells (Figure 8B) with calcium 4 dye in the presence or absence of test antibodies or isotype controls. Dye-loaded cells were incubated with Ramos and CEM cells at room temperature with 50 nM and 5 nM CXCL12, respectively. The area under the fluorescence curve between 20 and 200 seconds was quantified and the EC50 was calculated.

Figure 6B shows inhibition of CXCL12-induced calcium flux in CXCR4+ cells by anti-CXCR4 antibody MDX-1338 (BMS-936564) or anti-CXCL12 antibody. Calcium flux assays were performed by incubating Ramos cells (Figure 8A) or CEM cells (Figure 8B) with calcium 4 dye in the presence or absence of test antibodies or isotype controls. Dye-loaded cells were incubated with Ramos and CEM cells at room temperature with 50 nM and 5 nM CXCL12, respectively. The area under the fluorescence curve between 20 and 200 seconds was quantified and the EC50 was calculated.

Figure 7 shows the inhibition of the binding of 125I-labeled CXCL12 to CEM cells by the anti-CXCR4 antibody MDX-1338 (BMS-936564).