Multispecific antigen-binding molecules and uses thereof

A method of killing a breast cancer cell that expresses on its surface a PD-L1 molecule and a PRLR destroyer molecule, the method comprising the steps of:

• (i) contacting the breast cancer cell with an anti-PD-L1 bivalent monospecific antibody conjugated to a cytotoxic agent;
• and
• (ii) physically linking PD-L1 to PRLR on the breast cancer cell of part (i) by contacting the cell with an antibody that comprises (a) an antigen-binding fragment of an anti -PD-L1 antibody and (b) an antigen-binding fragment of an anti-PRLR antibody for simultaneous binding to PD-L1 and PRLR on the same cell,
• wherein the PD-L1 molecule and the cytotoxic agent are subsequently transported to a lysosome within the breast cancer cell through the physical linkage between the PD-L1molecule and the PRLR destroyer molecule.

A method of forcing PD-L1, expressed on the surface of a breast cancer cell, to degrade in a lysosome, comprising the step of physically linking PD-L1 to PRLR by contacting the breast cancer cell with an antibody that comprises (a) an antigen-binding fragment of an anti-PD-L1 antibody and (b) an antigen-binding fragment of an anti-PRLR antibody,

• wherein the antibody binds to PD-L1 and PRLR on the same breast cancer cell,
• wherein PD-L1 is transported to a lysosome through its physical linkage to PRLR and degraded, and
• wherein,
• in the presence of an inhibitor of protein synthesis, at least 40% of PD-L1 in the breast cancer cell is degraded after about 2 hours of contacting the breast cancer cell with the antibody, and/or
• in the presence of an inhibitor of protein synthesis, at least 80% of PD-L1 in the breast cancer cell is degraded after about 4 hours of contacting the breast cancer cell with the antibody.