Human Anti-CD274 Recombinant Antibody (clone 4736) (CAT#: HPAB-0261-YJ)

Figure 1 MEDI4736 binds specifically to PD-L1, inhibits its interactions with PD-1 and CD80 and does not trigger ADCC.

a. The signal derived in an ELISA from MEDI4736 binding to human PD-L1 or the related proteins B7-H3 and B7-DC.
b. The % specific binding observed between PD-1 and PD-L1 in a HTRF based ligand inhibition assay in the presence of increasing concentrations of MEDI4736 or an isotype control antibody.
c. The % specific binding observed between CD80 and PD-L1 in a HTRF based ligand inhibition assay in the presence of increasing concentrations of MEDI4736 or an isotype control antibody.
d. The level of NFAT driven luciferase activity in a CD16a transfected NK cell line following incubation with SKBR3 cells coated in MEDI4736 or a version of MEDI4736 bearing a wild type IgG1 Fc domain.

Stewart, R., Morrow, M., Hammond, S. A., Mulgrew, K., Marcus, D., Poon, E.,... & Bannister, D. (2015). Identification and characterization of MEDI4736, an antagonistic anti-PD-L1 monoclonal antibody. Cancer immunology research, 3(9), 1052-1062.

Figure 2 MEDI4736 overcomes PD-L1-mediated inhibition of T-cell activation.

a. The effect of increasing concentrations of MEDI4736 on a. thymidine incorporation 729 and b. IFNγ release in primary T cells stimulated with beads coated in anti-CD3, anti730 CD28 and either PD-L1 or irrelevant isotype control IgG. c. Thymidine incorporation in a mixed lymphocyte reaction in the presence of increasing concentrations of MEDI4736 or an isotype control antibody.

Stewart, R., Morrow, M., Hammond, S. A., Mulgrew, K., Marcus, D., Poon, E.,... & Bannister, D. (2015). Identification and characterization of MEDI4736, an antagonistic anti-PD-L1 monoclonal antibody. Cancer immunology research, 3(9), 1052-1062.

Figure 3 MEDI4736 shows anti-tumor activity in xenograft mouse models of human cancer.

a. Fluorescence observed on HPAC and A375 cell lines by flow cytometry following staining with an anti-PD-L1 (filled) antibody or an isotype control antibody (dotted)
b. HPAC tumor volumes (mm³) in NOD/SCID mice following co-implantation of primary human T cells and administration of MEDI4736 intraperitoneally at 5, 1, 0.1 and 0.01 mg/kg twice per week for 3 weeks as indicated. * = p≤0.05 as determined by a Mann-Whitney rank sum test.
c. A375 tumor volumes (mm³) in NOD/SCID mice following co-implantation of primary human T cells and administration of MEDI4736 intraperitoneally at 5, 1, and 0.1 mg/kg twice per week for 3 weeks as indicated.
d. A375 tumor volumes (mm³) in NOD/SCID mice without co-implantation of primary human T cells and administration of MEDI4736 intraperitoneally at 1, and 0.1 mg/kg twice per week for 3 weeks as indicated. * = p≤0.05 as determined by a Mann-Whitney rank sum test.

Stewart, R., Morrow, M., Hammond, S. A., Mulgrew, K., Marcus, D., Poon, E.,... & Bannister, D. (2015). Identification and characterization of MEDI4736, an antagonistic anti-PD-L1 monoclonal antibody. Cancer immunology research, 3(9), 1052-1062.