Friday, April 12
8:00 am Morning Coffee
8:25 Chairperson’s Opening Remarks
Limin Shang, Ph.D., Head, Exploratory Science Section,
Exploratory Science and Translational Medicine, NovImmune SA
8:30 Blockade of TLR4 Activation Represents a Promising
Strategy in Diabetes
Limin Shang, Ph.D., Head, Exploratory Science Section,
Exploratory Science and Translational Medicine, NovImmune SA
Dysregulation of Toll-like receptor 4 (TLR4) signaling via
numerous ligands appears to play an underlying role in the pathogenesis of
multiple inflammatory diseases. Thus, NI-0101, an anti-human TLR4 monoclonal
antibody, was generated to have the capacity to interfere with LPS-induced
signaling of TLR4 as well as other activators (i.e., endogenous or chemical
ligands). To evaluate the role of TLR4 in beta islet cell biology, NI-0101 was
shown to block human islet-induced immune cell activation. Furthermore, using
an anti-mouse TLR4 mAb in vivo, blockade of TLR4 was efficient in protecting
grafted islets from rejection in a mouse islet transplantation model as well as
in murine models of diabetes. Taken together, these data promote blockade of
TLR4 activation as a promising strategy in diseases associated with islet cell
pathogenesis.
9:05 Therapeutic Antibody against Toll-Like Receptor 3 (TLR3)
for the Treatment of Inflammation
Carine Paturel, Ph.D., Director, R&D, Innate Pharma
Innate Pharma is developing a therapeutic antibody against
Toll-like Receptor 3 (TLR3), an immune checkpoint controlling inflammation. We
have generated a panel of mouse anti-human TLR3 antibodies and humanization of
several candidates is ongoing. In addition, Innate Pharma generated efficacy
data in animal models of COPD, Colitis, Rheumatoid Arthritis and sepsis with
surrogate rat anti-mouse TLR3.
9:40 Mechanisms of HIV-Mediated Inhibition of TLR4 Triggered
Macrophage Activation
Souvenir Tachado, M.D., Assistant Professor, Medicine, Beth
Israel Deaconess Medical Center
Alveolar macrophages (AM) express Toll-like receptors (TLRs)
such TLR4, and we found significant derangement of TLR4-mediated activation of
AM from asymptomatic HIV+ subjects. Furthermore, this derangement is specific,
may represent AM reprogramming to an LPS-tolerant phenotype and is independent
of HAART. In summary, HIV infection of AM results in targeted and specific
impairment of macrophage TLR-mediated signaling pathways, impairing critical
components of first line host defenses in the lungs.
10:15 Coffee Break with Exhibit and Poster Viewing
10:55 Development of a TLR7 Agonist to Treat Chronic Hepatitis
B Virus (HBV) Infection
Simon Fletcher, Ph.D., Principal Scientist, Biology, Gilead
Sciences
GS-9620 is a potent, selective agonist of human TLR7 being
developed to treat chronic HBV (CHB). It has demonstrated promising antiviral
activity in both the woodchuck and chimpanzee models of CHB, and single dose
safety has been demonstrated in healthy volunteers. Data from these preclinical
and clinical studies will be presented.
11:30 A Critical Role for Calcium Mobilization in Activation of the NLRP3 Inflammasome
Tiffany Horng, Ph.D., Assistant Professor, Department of Genetics and Complex Diseases, Harvard School of Public Health
The NLRP3 inflammasome mediates production of inflammatory mediators such as IL-1b and IL-18 and as such is implicated in a variety of inflammatory processes including infection, sepsis, autoinflammatory diseases and metabolic diseases. The proximal steps in NLRP3 inflammasome activation are not well understood. Here we elucidate a critical role for Ca2+ mobilization in activation of the NLRP3 inflammasome by multiple stimuli. We demonstrate that blocking Ca2+ mobilization inhibits assembly and activation of the NLRP3 inflammasome complex, and that Ca2+ signaling is pivotal in promoting mitochondrial damage. Our findings support a model for NLRP3 inflammasome activation by Ca2+-mediated mitochondrial damage.
12:05 Luncheon Presentation (Sponsorship Opportunity
Available) or Lunch on Your Own
1:45 Chairperson’s Remarks
Robert Hershberg, M.D., Ph.D., CEO, VentiRx Pharmaceuticals
1:50 TLR3-Expressing Tumor Parenchyma and Infiltrating NK
Cells Promote Tumor Control in Hepatocellular Carcinoma
Valerie Chew, Ph.D., Research Scientist, Tumor Immunology
(JPA) Lab, Singapore Immunology Network
Our work features the latest findings with convincing data
about the role of TLR3 in controlling HCC. Our data is derived from in vitro,
in vivo with HCC mouse models as well as from 172 HCC patients from Singapore,
Hong Kong and Zurich.
2:25 The Significance of Toll-Like Receptor-9 in Triple
Negative Breast Cancer
Katri Selander, M.D., Ph.D., Assistant Professor, Medicine,
University of Alabama at Birmingham
TLR9 is an innate immunity DNA-receptor which is also widely
expressed in various cancers. We demonstrated recently that low tumor TLR9
expression is a poor prognosis marker specifically in triple negative breast
cancer. The aim of our continuing work is to characterize at the molecular
level how the lack of tumor TLR9 promotes poor survival in these patients.
2:55 The Unique Biology and Clinical Relevance of Toll-Like
Receptor 8
Robert Hershberg, M.D., Ph.D., CEO, VentiRx Pharmaceuticals
The biology of TLR8 is unique in humans given its expression
on myeloid-derived dendritic cells, monocytes and NK cells. In addition, TLR8
can be targeted using small molecule agonists and antagonists. Preclinical and
clinical data are emerging which highlight TLR8 as an important target in human
disease.
3:30 POSTER SPOTLIGHT Inflammasomes Are Important Mediators of Bladder Inflammation
Francis M. Hughes, Jr., Ph.D., Medical University of South Carolina
4:05 End of Conference