CD7-DE-vcMMAE

CD7-DE-vcMMAE is a novel Fc-optimized antibody-drug conjugate (ADC) targeting the CD7 antigen, which is highly expressed in various T-cell acute lymphoblastic leukemia (T-ALL) subtypes, including early T-cell precursor (ETP)-ALL. The ADC features a CD7-specific antibody engineered with two amino acid substitutions (S239D/I332E, the "DE-variant") in the Fc-domain to enhance its affinity for activating Fcγ receptors (FcγRIIa and FcγRIIIa), thereby boosting antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). This antibody is conjugated to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via an enzymatically cleavable valine-citrulline (vc) linker. CD7-DE-vcMMAE demonstrates a multi-modal mechanism of action: it induces G2/M cell cycle arrest and apoptosis upon internalization, facilitates bystander killing of neighboring CD7-negative cells, and triggers potent immune effector cell-mediated killing. Preclinical studies in xenograft and patient-derived xenograft (PDX) models of T-ALL have shown significant tumor growth reduction and improved survival outcomes.