The DXD monoclonal antibody is created using the hybridoma technique. Immunizing a mouse with DXD-BSA induces antibody production by B cells. B cells are extracted from the mouse and then fused with myeloma cells to form hybridomas, from which DXD-specific antibody-producing ones are screened. Selected hybridomas are cultured to generate DXD monoclonal antibodies, which are harvested and subjected to affinity chromatography purification. The purity of the antibody exceeds 90% by SEC-MALS. The antibody's activity has been validated in different functional ELISA, showing the EC50 of 1.840 to 2.253 ng/mL, 2.365 to 2.835 ng/mL, 2.225 to 2.851 ng/mL with ADC-1 (DXD), ADC-2 (DXD), T-DXd (DS-8201), respectively. This DXD monoclonal antibody is a potent tool for DXD-based ADC research, especially for positive reference of DXD-ADC preclinical/clinical immunogenicity, PK analysis, and qualitative detection of DAR value, helping to evaluate and control the efficacy and safety of DXD-ADC drugs.
The Exatecan derivative DXD (deruxtecan) is a cytotoxic payload used in the DXD-ADC (antibody–drug conjugate) technology, an innovative strategy in the field of targeted drug delivery particularly for cancer therapy. DXD-ADC is directed to targeted tumor cells via antibody-tumor cell-sepcific antigen interaction. After that, ADC undergoes internalization and subsequent processing, leading to the release of the cytotoxic DXD. DXD inhibits topoisomerase I (TOP1) activity and leads to the apoptosis of targeted cancer cells. DXD shows 10-fold higher DNA TOP1 activity inhibitory potency than the active metabolite of irinotecan SN-38. Due to its high cell membrane permeability, DXD exerts a bystander antitumor effect, also providing efficient killing of heterogeneous tumor cells. DXD can reduce cross-resistance, has good water solubility, and can form a stable high-DAR (drug-to-antibody ratio) value in ADC for each target. DXD also has a relatively short systemic half-life in the blood and can be excreted faster outside the body, which helps reduce the risk of adverse reactions.
