Abstract: This application relates to isolated antibodies, or antigen-binding fragments thereof, that bind to at least one isoform of cluster of differentiation 97 (CD97), also known as adhesion G protein-coupled receptor E5 (ADGRE5), antibody-drug conjugates comprising such antibodies or antigen-binding fragments, as well as polynucleotides and vectors that encode for such antibodies or antigen-binding fragments. This application further relates to methods of producing the antibodies or antigen-binding fragments and using the antibodies or antigen-binding fragments for treatment of diseases.