Identification of CADM1 as an Immunotherapeutic Target and Evaluation of a Novel CADM1-Targeting Antibody-Drug Conjugate in Preclinical Osteosarcoma Models

Due to the paucity of validated cell surface osteosarcoma-specific targets, patients with this condition have long been excluded from the benefits of antibody-drug conjugate (ADC) therapy observed in several solid and hematologic malignancies. Our comprehensive surfaceome and RNA-seq profiling approach identified osteosarcoma-specific cell-surface antigens that are highly expressed in osteosarcomas but minimally expressed in normal tissues. As a result, one such antigen, CADM1, was selected for the generation of an ADC. Overall design: To identify osteosarcoma-specific cell-surface antigens that are highly expressed in osteosarcomas, 17 osteosarcoma cell lines were used to perform RNA-seq, and gene expression profiling was analyzed using 150-bp paired-end RNA-seq, achieving an average coverage of 26.5 million reads per sample (range, 23.3–29.4 million reads).