Main Conference Day 3Wednesday, 17 December 2025 - PT (Pacific Time, GMT-08:00)

The ion channel Kv1.3 is well known to be important in the activation of effector-memory T cells. We have developed a unique ultralong CDR3 antibody based on the cow scaffold that potently inhibits Kv1.3 activity. Surprisingly, this reagent was also found to inhibit important immune functions in monocytes and macrophages, revealing a novel role for Kv1.3 in the innate immune system.

Inflammation and tissue fibrosis co-exist and are causally linked to organ dysfunction. However, the molecular mechanisms driving immune-fibroblast crosstalk remain unexplored, and there are currently no approved treatments that directly target cardiac fibrosis. Using human tissues and mouse models, we delineate the functions of FAP+ fibroblasts within the heart and define immune cell crosstalk and transcriptional events that govern their differentiation. From a broader perspective, we show that bispecific T-cell engaging antibodies targeting FAP+ fibroblasts suppress cardiac fibrosis and have similar effects in other organs. These findings highlight the therapeutic potential of cell specific targeting of defined fibroblasts subsets.

We have previously demonstrated that an IgG3 agonistic TLR4/MD2 antibody reversed acute murine Type 1 Diabetes (T1D) through induced immune tolerance. To translate this work to humans we developed novel human TLR4 agonistic antibodies, demonstrated that the IgG3 isotype and enhanced multivalency are necessary for their TLR4 signaling, and demonstrated their tolerogenic potential for treating inflammatory diseases.

We leverage our discoveries which show that blockade of innate immune regulatory pathways can halt and even reverse lung fibrosis. We aim to develop novel, multivalent Ab constructs that simultaneously block the activity of these profibrotic pathways.

The inability of diverse biomolecules to readily penetrate the blood-brain barrier is a key limitation to their use in research, diagnostic, and therapeutic applications. We are developing bispecific antibodies that engage either CD98hc or transferrin receptor, and efficiently transport biomolecules into the CNS. We will discuss our recent work on protein delivery to the CNS, including cytokines for modulating the immune environment in the brain for therapeutic applications.

Natriuretic peptide receptor 1 (NPR1) is a membrane-bound guanylate cyclase and activated by atrial (ANP) and brain (BNP) natriuretic peptide and NPR1 agonism alters blood pressure via regulation of intravascular volume, vasorelaxation, natriuresis and diuresis. We have isolated fully human antibodies from VelocImmune® mice that either agonize or antagonize NPR1 activity and are developing as potential treatment of cardiac diseases such as heart failure and hypovolemic/hypotensive disorders.