ntKD033

ntKD033 is a non-targeting immunocytokine developed by Kadmon (now a subsidiary of Sanofi) as a control molecule to investigate the mechanism of action of the PD-L1-targeted immunocytokine KD033. It consists of a non-binding human IgG1 monoclonal antibody fused at the C-terminus to a human interleukin-15 (IL-15) and IL-15 receptor alpha (IL-15Rα) sushi domain complex. The antibody scaffold contains LALA mutations (L234A/L235A) in the Fc region to minimize antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity. While ntKD033 lacks the ability to target programmed death-ligand 1 (PD-L1) in the tumor microenvironment, it retains the biological activity of the IL-15/IL-15Rα complex, acting as a systemic agonist that stimulates the proliferation and activation of natural killer (NK) cells and memory CD8+ T cells. In preclinical studies, ntKD033 was used to demonstrate that the superior anti-tumor efficacy and tolerability of KD033 are dependent on its specific localization to the tumor microenvironment, as ntKD033 treatment resulted in higher systemic immune activation and associated toxicities compared to the targeted version.

Other names

non-targeting KD033