The present disclosure provides antibody-drug conjugates (ADCs) comprising a cytotoxic or cytostatic agent linked to an anti-EGFR antibody by way of a linker, compositions comprising the ADCs, methods of making the ADCs, and methods of treating a cancer comprising administering the ADCs to a subject having cancer. The present disclosure provides ADCs that specifically bind EGFR, and in particular human EGFR (hEGFR). The anti-EGFR Ab described herein comprises a S239C mutation in a heavy chain constant region, wherein the numbering is in accordance with Kabat. In certain embodiments, the heavy chain constant region of the anti-EGFR antibody either lacks a C-terminal lysine or comprises an amino acid other than lysine at a C-terminus of the heavy chain constant region.
