Targeting prostate cancer with site-specific antibody-drug conjugates enabled by tandemly fused ADP-ribosyl cyclases.

ABSTRACT: Antibody-drug conjugates (ADCs) bring superior efficacy and safety profiles to the clinic by harnessing the power of biologics and chemotherapy. Despite numerous ADCs at different preclinical and clinical stages, homogeneous ADC with increased numbers of payloads conjugated at specific positions are still desired for enhanced pharmacological properties. To generate site-specifically conjugated ADCs with greater drug-to-antibody ratios (DARs), monoclonal antibodies targeting prostate-specific membrane antigens (PSMA) were genetically fused with tandem CD38 enzymes, a member of the ADP-ribosyl cyclase family. The resulting antibody-CD38 fusions coupled with its dinucleotide substrate-derived drug linker facilitate generation of ADP-ribosyl cyclase-enable ADCs (ARC-ADCs) carrying 2, 4, 6, and

SUBMITTER: Zhang L 

PROVIDER: S-EPMC12286717 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature