Advanced Course in Immunology On Demand Lecture Recordings-Drug Discovery and Development: Immunotherapeutics for Autoimmune Disease

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The speaker, an immunologist with a long biotech career, described how her work evolved from basic mouse immunology to translating autoimmune disease biology into therapeutics. She emphasized that drug discovery is slow, expensive, and full of setbacks, but can be highly rewarding when a therapy reaches patients.<br /><br />Her first major story focused on a BDCA2 antibody program targeting plasmacytoid dendritic cells (PDCs) in lupus. Because PDCs drive type 1 interferon production, and lupus shows a strong interferon signature, she pursued an antibody to BDCA2, a receptor uniquely expressed on human PDCs. Along the way, the team discovered several unexpected mechanisms: the antibody caused receptor internalization and, importantly, also reduced the Fc-gamma receptor needed for immune-complex signaling. This turned out to be beneficial. After extensive testing in recombinant systems, whole blood, lupus patient samples, and non-human primates, the candidate showed biomarker and clinical activity and advanced into late-stage trials.<br /><br />Her second story described a newer program at Seismic Therapeutic aimed at creating a PD-1 agonist for autoimmune disease. The goal was to restore immune tolerance by activating PD-1 while avoiding depletion of Tregs and avoiding pro-inflammatory Fc receptor signaling. The team designed a bifunctional antibody with a low-affinity PD-1 binding arm and an Fc region selectively engaging inhibitory Fc-gamma R2B. Using machine learning, structural analysis, and functional assays, they selected a candidate that preserves PD-1 on the cell surface, reduces inflammatory cytokines, and entered healthy volunteer trials in 2024.<br /><br />Overall, the talk highlighted the complexity of translating immune targets into drugs and the importance of mechanism, biomarkers, and careful model selection.

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Lecture 21: Joanne L. Viney, Seismic Therapeutic

Drug Discovery and Development: Immunotherapeutics for Autoimmune Disease

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Joanne L. Viney, Seismic Therapeutic Drug Discovery and Development: Immunotherapeutics for Autoimmune Disease

Keywords

immunology

biotech

autoimmune disease

drug discovery

lupus

BDCA2 antibody

plasmacytoid dendritic cells

type 1 interferon

Fc-gamma receptor

PD-1 agonist

immune tolerance

bifunctional antibody

machine learning