Figure 7.

Targeted killing of PD‐1–positive HIV‐infected cells. PD‐1 expressing CD4 T cells represent the primary compartment of HIV‐infected cells that produce replication competent virus. Targeted killing of these PD‐1 positive cells represents a novel therapeutic strategy that can deplete the HIV reservoir of infected cells. Antibody drug conjugates (ADC) use a toxin‐conjugated antibody that binds to the cell surface PD‐1 receptor. Internalization of PD‐1 results in ADC degradation within the lysosome, resulting in toxin release that specifically kills the PD‐1 expressing cell. An alternate strategy for the targeted killing of HIV infected PD‐1 positive cells is through antibody‐dependent cellular cytotoxicity (ADCC) with an IgG1 anti‐PD‐1 antibody. The Fc portion of the antibody binds to the FcγRIII receptors expressed on effector cells including natural killer (NK) cells. NK cells release cytotoxic granules that kill the PD‐1–positive HIV‐infected CD4 T cell