cantuzumab ravtansine (IMGN242) / AbbVie - LARVOL DELTA

IKS04, an antibody drug conjugate with a highly potent DNA crosslinker payload for the treatment of gastrointestinal cancers (AACR 2025) - "The ADC was active against gastric and colorectal cancer xenograft models at single doses of 0.5 to 1 mg/kg, while the maytansinoid-based ADC benchmark cantuzumab ravtansine was inactive even at 2 mg/kg. Consistent with this concept, co-administration of the unconjugated antibody with the ADC at a 5 to 50-fold excess improved the minimally effective dose in the CA242-high SNU16 gastric and HT29 colon cancer models compared to ADC alone while the antibody itself had no anti-tumor activity.IKS04 is an ADC with a DNA crosslinker payload that shows potent in vitro and in vivo efficacy against gastric and colorectal cancer tumor models. Co-administration of the unconjugated antibody can improve ADC delivery which drives increased efficacy in preclinical models without increasing toxicity."

ADC • Colon Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Bottom-Up Protein Analysis Workflow for Simultaneous Characterization of Payloads, Disulfide Bonds, and Free Thiols in Antibody-Drug Conjugates. (PubMed, Anal Chem) - "Using trastuzumab emtansine as a model system, our workflow enables the identification of 46 payload-conjugated sites and 100% disulfide coverage, comparable to results from a conventional bottom-up analysis using two separate LC-MS pipelines. For cantuzumab ravtansine, which contains a spatially hindered disulfide bond in the linker, we have achieved comprehensive mapping of both payload-conjugated sites and disulfide bonds. This workflow has been further applied to quantify free thiol at cysteine residues and linker-payload disulfide bonds for model ADCs under reductive stress, revealing the distinct stability of the disulfide bonds in different structural regions."

Journal