Avidimab15 Sep 2025 08:06
TF,
complicated but Avidimab can be used for direct killing. IgG3 antibodies, particularly when engineered, can induce direct cell killing through a process involving Fc-Fc self-association and subsequent enhanced avidity. https://pmc.ncbi.nlm.nih.gov/articles/PMC7611157/
DAC have advantages over ADCs.
Degrader-antibody conjugates (DACs) are an emerging class of biotherapeutics that combine the high specificity of antibodies with the catalytic mechanism of targeted protein degradation. In these conjugates, a monoclonal antibody or an antigen-binding fragment is chemically linked to a small-molecule degrader. The degrader moiety typically includes a ubiquitin E3 ligase binding group (E3LB) and a protein binding group (PB) that, together, recruit the cellular ubiquitination machinery to label a target protein for proteasomal degradation. Once the antibody binds its specific cell-surface antigen, the entire conjugate is internalized into the cell where the degrader is liberated (often via cleavable linkers) and then orchestrates the elimination of disease-causing proteins. In essence, this technology leverages the well‐established antibody targeting mechanism and extends its functionality into the realm of intracellular protein clearance, often overcoming limitations presented by conventional small molecules or even antibody–drug conjugates (ADCs).
Importance in Drug Development
The significance of DACs in modern drug development rests on several pillars. First, by harnessing the catalytic nature of protein degraders, these conjugates can induce the complete and sustained elimination of oncogenic or other pathogenic proteins. This may be particularly useful when the target is traditionally considered “undruggable” by classical inhibition strategies. Second, the dual functionality allows for improved cell-specific delivery and intracellular activity, which can lead to a widening of the therapeutic window by reducing systemic toxicity. In cancers and potentially other diseases, the precise degradation of disease-driving proteins has opened new avenues for therapeutic intervention by combining two mechanisms into one therapeutic entity: the targeting ability of antibodies and the potent, catalytic effect of degraders. Finally, this approach provides opportunities to overcome issues associated with resistance mechanisms as degraders can eliminate rather than merely inhibit targeted proteins, potentially offering longer-lasting responses in patients.
Scancell is targeting TRIM21;
Targeting TRIM21 for degradation involves two main approaches: using TRIM21 to degrade oncogenic targets (like c-Myc or PRMT1) or developing drugs that trigger TRIM21-mediated degradation of cancer-driving proteins. For instance, TRIM21 degrades the oncogene PRMT1 in colorectal cancer and c-Myc in KRAS-mutant colorectal cancer to suppress tumor growth.
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