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Notch-ADC (Notch-antibody drug conjugate) is a class of antibody-drug conjugates designed to target Notch receptors, which are overexpressed or amplified in various human cancers. Developed by Pfizer, these ADCs combine high-affinity anti-Notch monoclonal antibodies with cytotoxic payloads, specifically novel tubulin inhibitors, via cleavable or non-cleavable linkers. Unlike traditional gamma-secretase inhibitors or unconjugated antibodies that block Notch signaling, Notch-ADCs utilize the specificity of the antibody to deliver the cytotoxic payload directly into Notch-expressing tumor cells, inducing cell death regardless of whether the tumor is driven by active Notch signaling. In preclinical models, Notch-ADCs have demonstrated potent in vitro growth inhibition and sustained in vivo tumor regression in lung, breast, gastric, and ovarian cancer xenografts.
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