DVD-IgG1 antibody-drug conjugates: Expanding the landscape of targeted cancer therapy.

Antibody-drug conjugates (ADCs) are transforming targeted cancer therapy, yet conventional IgG-based formats are often limited by stochastic conjugation, yielding heterogeneous ADCs. Dual-variable domain IgG1 (DVD-IgG1) antibodies offer a modular solution by enabling precise, site-specific conjugation through the catalytic lysine and engineered arginine or cysteine residues, affording homogeneous ADCs. This review summarizes recent advances in DVD-IgG1-based ADCs, highlighting site-specific conjugation, compatibility with diverse linker chemistries, and incorporation of both established and experimental payloads. Together, these developments position DVD-IgG1s as a versatile platform to expand the chemical and biological design space of next-generation ADCs.