NeuroMab™ Anti-CXCR4 BBB Shuttle Antibody(NRZP-1022-ZP3798)

Figure 1 shows the inhibition of the binding of 125I-labeled CXCL12 to CEM cells by the anti-CXCR4 antibody MDX-1338 (BMS-936564).

Figure 2 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 Ramos 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 3 shows the inhibition of Ramos tumor cell proliferation in vivo in a subcutaneous tumor model by anti-CXCR4 human antibodies F7 (BMS-936564) and F9.

Graphs show mean tumor volume growth curves.

Figure 4A shows the results of an apoptosis assay performed by incubating Ramos cells with 10 μg/mL MDX-1338 (BMS-936564) or an isotype control for 24 hours at 37°C. Cells were stained with Annexin V-FITC and propidium iodide.

Figure 4B shows the results of an apoptosis assay performed by incubating Ramos cells with 10 μg/mL MDX-1338 (BMS-936564) or an isotype control for 24 hours at 37°C. The percentage of cells positive for Annexin V only or both Annexin V and PI was determined.

Figure 5 shows that the induction of apoptosis by MDX-1338 (BMS-936564) is CXCR4 specific. MDX-1338 or an isotype control was added to CXCR4-transfected 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 6 shows the in vivo tumor growth inhibition of Ramos cell lymphoma xenografts by the CXCR4-blocking antibody MDX-1338 (BMS-936564) and a positive control of rituximab (a chimeric anti-CD20 monoclonal antibody), and no tumor growth inhibitory effect of blocking anti-CXCL12 antibodies.

Figure 7A shows the in vivo tumor growth inhibition of HL60 cell acute myeloid leukemia xenografts by MDX-1338 (BMS-936564). Cytarabine is not expected to inhibit tumor growth in cytarabine-resistant Nomo-1 tumors.

Figure 7B shows the in vivo tumor growth inhibition of Nomo-1 (Figure 17B) acute myeloid leukemia xenografts by MDX-1338 (BMS-936564). Cytarabine is not expected to inhibit tumor growth in cytarabine-resistant Nomo-1 tumors.

Figure 8A 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 MOLP8 cell xenografts treated with MDX-1338 alone or in combination with lenalidomide or bortezomib;

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

B, Tumor growth inhibition of JJN-3R cell xenografts treated with MDX-1338 or lenalidomide or bortezomib

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

Panel C, Tumor growth inhibition of parental JJN-3 cell xenografts treated with MDX-1338 alone or in combination with bortezomib.

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

Panel D, Tumor growth inhibition of parental JJN-3 cell xenografts treated with MDX-1338 alone or in combination with lenalidomide

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

Panel E, Tumor growth inhibition of MDX-1338 alone or in combination with lenalidomide (REVLIMID®) in RPMI-8226 cell xenografts

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

Panel F, Tumor Growth Inhibition of MDX-1338 Alone or in Combination with Bortezomib (VELCADE®) in RPMI-8226 Cell Xenografts