Main Conference Day 1Monday, 15 December 2025 - PT (Pacific Time, GMT-08:00)

The antibody molecule is a wonder of nature that connects disease targets with immune effector cells via its Y-shaped topology of three domains connected by a hinge region. We describe GEM-DIMER technology allowing us to create superdimers of two antibodies interconnected at their hinge regions by a strong non-covalent interaction. Our superdimers demonstrate cooperative binding to disease targets and immune effector cell receptors, making them ideal for human therapeutic applications.

The efficiency of complement activation among IgG subclasses is primarily determined by their capacity to form oligomers upon binding to antigens. This oligomerization facilitates the multivalent engagement of the C1 complex, thereby initiating the classical complement pathway. These insights offer a mechanistic understanding that could inform the design of antibody therapies with enhanced effector functions.

Antibodies have broad utility in imaging, targeted gene delivery, and disease therapy, and many of these applications require conjugation to secondary molecules. Unfortunately, conventional conjugation approaches are limited by destabilization of structure, heterogeneity, and technically demanding multi-step reactions. To overcome these challenges, we developed a straightforward and highly general platform for site-specific antibody conjugation that blends metabolic glycoengineering with protein design, presenting a highly efficient strategy to produce antibody conjugates.

Antibodies targeting human cytomegalovirus (CMV) exhibit limited efficacy due to immune evasion mechanisms, including viral receptors that capture human Fc domains. We engineered Fc variants that retain binding to host receptors but exhibit markedly reduced binding to viral Fc receptors. Antibodies with engineered Fc domains mediated enhanced CD16A activation and limited viral spread in CMV-infected fibroblasts more effectively than wild-type Fc.