Undisclosed cell-surface antigen and intracellular protein-of-interest targeted for degradation

The term "Undisclosed cell-surface antigen and intracellular protein-of-interest targeted for degradation" refers to a therapeutic strategy rather than a specific biological target. This approach typically involves a bifunctional molecule, such as an Antibody-Degrader Conjugate (ADC) or a multispecific degrader (e.g., AbTAC or LYTAC), designed to localize to a specific cell type via a surface antigen and subsequently induce the degradation of an intracellular protein-of-interest (POI) [Paiva & Crews, 2019; Orum Therapeutics, 2024]. This modality, often referred to as Targeted Protein Degradation (TPD), leverages the cellular ubiquitin-proteasome system or lysosomal pathways to eliminate proteins that are otherwise difficult to inhibit with traditional small molecules [Paiva & Crews, 2019; He et al., 2022]. By using a cell-surface antigen as a "zip code," these therapies aim to improve the therapeutic index of potent degrader payloads, such as PROTACs or molecular glues, by restricting their activity to target-positive cells [Orum Therapeutics, 2024]. Because the specific identities of the antigen and the POI are not provided, the biological function, disease relevance, and safety profile are dependent on the specific molecular pair chosen for development [He et al., 2022]. This terminology is frequently used in early-stage drug development or patent filings to describe a platform technology or a candidate whose specific targets remain proprietary. Consequently, while the mechanism of action is well-defined as a form of TPD, the clinical application is typically focused on oncology where high-precision targeting of intracellular drivers is required [Paiva & Crews, 2019].

Other names

Targeted Protein Degradation (TPD) pairAntibody-Degrader Conjugate (ADC) targetBifunctional degrader targetPROTAC-ADC target

Targeted protein degradation (TPD) via a bifunctional modality that utilizes a cell-surface antigen for cell-specific delivery or recruitment to induce the degradation of an intracellular protein-of-interest.