ZEA-αCD4

ZEA-αCD4 is an experimental antibody-drug conjugate (ADC) designed to modulate the tumor immune microenvironment, specifically in the context of hepatocellular carcinoma (HCC). The ADC consists of an anti-CD4 monoclonal antibody conjugated to a zearalenone (ZEA) payload. Zearalenone is a ligand with high affinity for Macrophage Scavenger Receptor 1 (MSR1). The therapeutic strategy involves using the anti-CD4 antibody to deliver and tether ZEA onto the surface of CD4+ T cells. This prevents MSR1+ tumor-associated macrophages from interacting with Integral Membrane Protein 2A (ITM2A) on the T cells. By blocking the MSR1-ITM2A interaction, ZEA-αCD4 prevents the disruption of the ITM2A-ZAP70 signaling axis, thereby averting CD4+ T cell exhaustion and restoring antitumor immune responses. Preclinical studies have demonstrated that ZEA-αCD4 can effectively inhibit tumor growth and enhance the efficacy of PD-L1 checkpoint inhibitors.