This application discloses anti-PMEL17 antibodies, antigen binding fragments thereof, and antibody drug conjugates comprising antibodies or antigen binding fragments conjugated to a GNAQ/GNA11 inhibitor. The application also discloses methods of treating or preventing cancer using the antibodies, antigen binding fragments, and antibody drug conjugates. Also disclosed herein are methods of making the antibodies, antigen binding fragments, and antibody drug conjugates, and methods of using the antibodies and antigen binding fragments as diagnostic reagents.