Thursday, April 11
7:30 am Registration and Morning Coffee
8:25 Chairperson’s Opening Remarks
Mark J. Paul-Clark, Ph.D., Lecturer in Cardiothoracic Pharmacology, National Heart & Lung Institute, Imperial College
8:30 Inflammatory Monocytes Activate Memory CD8+ T and Innate NK Lymphocytes in an Inflammasome and Type I-Dependent Manner during Microbial Pathogen Invasion
Gregoire Lauvau, Ph.D., Associate Professor, Microbiology and Immunology, Albert Einstein College of Medicine
Our work shows that Ly6C+CCR2+ inflammatory monocytes, a subset of monocytes, largely orchestrate memory CD8+ T and NK lymphocyte activation by differentiating into interleukin-18 (IL-18)- and IL-15-producing cells in an inflammasome and type I interferon-IRF3-dependent manner. Memory CD8+ T cells became potent effector cells by sensing inflammation from monocytes independently of their cognate antigen. Like NK cells, they underwent rapid mobilization, upregulated intense and sustained effector functions during bacterial, viral and parasitic infections, and contributed to innate responses and protection in vivo.
9:05 Inhibition of Specific Endosomal Toll-like Receptors: A Novel Approach to the Treatment of Autoimmune Diseases
Robert Arbeit, MD, Vice President of Clinical Development, Idera Pharmaceuticals
Idera is developing candidates which inhibit specific endosomal Toll-like receptor-mediated immune activation. Two agents are currently in development for the treatment of autoimmune diseases: IMO-3100, a TLR7 and 9 antagonist, and IMO-8400, a TLR7, 8, and 9 antagonist. A recently completed Phase 2a proof-of-concept trial of IMO-3100 in psoriasis successfully demonstrated the therapeutic effect of TLR antagonists in autoimmune disease.
9:40 Recombinant Surfactant Protein SP-D as a Therapeutic in Lung Inflammation and Allergy
Uday Kishore, Professor, Director, Centre for Infection, Immunity and Disease Mechanisms, Brunel University
SP-D is a lung collectin that has anti-allergic and anti-microbial properties. We have shown that recombinant SP-D can suppress allergic asthma in mouse models via suppression of IgE synthesis, histamine release, eosinophilia, inflammation and Th2 response. We now understand the immunological mechanisms through which SP-D modulates eosinophils, dendritic cells, T and B cells. These studies have now led to setting up of clinical trials.
10:15 Coffee Break with Exhibit and Poster Viewing
10:55 Transcriptome Analysis of Cigarette Smoke Extract Induced TLR2-Dependent Activation of Human Cells
Mark J. Paul-Clark, Ph.D., Lecturer in Cardiothoracic Pharmacology, National Heart & Lung Institute, Imperial College
We have previously shown that oxidants and cigarette smoke extract (CSE) activate cells in vitro and in vivo, in part via the pattern recognition receptor TLR2. Transfected HEK293 cells with TLR2/6 or control vector were treated with H2O2, CSE and control media for 8h. Expression patterns in HEK293 cells were similar to those obtained from THP-1 cells and PBMCs. Pathway analysis of these cells revealed that inflammation was associated with NRF2-mediated and aryl hydrocarbon receptor signaling pathways. The study suggests that chronic pathologies caused by smoking cigarettes are driven by persistent episodes of inflammation and oxidative stress and also provides a gene list for the cellular response to oxidants.
11:30 A Nonredundant Role for Tlr9 and the Nalp3 Inflammasome in Acetaminophen-Induced Liver Injury
Wajahat Z. Mehal, Ph.D., Associate Professor, Section of Digestive Diseases, Yale University
12:05 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
1:45 Chairperson’s Remarks
Anshu Agrawal, Ph.D., Associate Adjunct Professor, Medicine/Immunology, University of California Irvine
1:50 Activation of Cytosolic Pathogen Sensor RIG-I for Prophylactic and Therapeutic Applications against Infectious Diseases
Prakash Sambhara, D.V.M., Ph.D., Chief, Immunology Section, Influenza Division, Centers for Disease Control and Prevention
Retinoic acid-inducible gene-I (RIG-I) is a pattern recognition receptor that is present in the cytosol. Interaction of RIG-I with its ligand leads to the activation of type 1 interferon. Type 1 interferon plays a major role in the induction of antiviral immunity by activating interferon responsive gene families. I will discuss latest developments with RIG-I and its ligands, and their utility as antiviral agents and adjuvants.
2:25 Development of STING-Specific Cyclic Dinucleotide Adjuvants for Cancer and Infectious Disease Vaccines
Thomas Dubensky, Jr., Ph.D., CSO, Aduro Biotech
Cyclic dinucleotides (CDNs) are bacterial intracellular messengers that have been shown to also function as PAMPs (Pathogen Associated Molecular Patterns) that activate innate immunity through triggering the mammalian host cell protein STING (Stimulator of Interferon Genes). Direct binding of CDNs to STING initiates a signaling cascade through the TBK-1/IRF-3 axis to induce type I interferon and other co-regulated genes. We demonstrate that vaccination with CDN-adjuvanted recombinant protein formulated to facilitate cytosolic trafficking induced STING-dependent, antigen-specific CD4 and CD8 T cell responses, together with Th1-based antibodies correlated with protective immunity in a viral challenge model. When co-formulated with an irradiated GM-CSF secreting tumor cell vaccine (STINGVAX) to mobilize and activate dendritic cells in vivo, CDNs promoted a significant reduction of tumor growth in a stringent B16 melanoma treatment model. STING represents a significant new adjuvant target for the development and clinical translation of effective vaccines for infectious and malignant diseases.
2:55 Talk Title to be Announced
Andreas Muhs, Ph.D., CSO, AC Immune SA
3:30 Refreshment Break with Poster and Exhibit Viewing
4:05 Therapeutic Potential of Dectin-1 Agonists
Anshu Agrawal, Ph.D., Associate Adjunct Professor, Medicine/Immunology, University of California Irvine
Beta glucans, found in natural products such as mushrooms, oat, and fungi can activate the dendritic cells of the immune system via the dectin-1 receptor which belongs to the family of C-type lectin receptors. Activation of dendritic cells via dectin-1 results in the generation of Th17, cytotoxic CD8 T cell and B cell IgA production. These responses are highly effective against cancer as well as against mucosal infections.
4:40 Moderated Breakout Discussion Groups
Potential use of of Dectin-1 agonists (beta glucans) as anti-cancer, anti-fungal and vaccine adjuvants.
Moderator: Anshu Agrawal, Ph.D., Associate Adjunct Professor, Medicine/Immunology, University of California Irvine
• Present status of anti-cancer therapy with dectin-1 agonists- limitations and solutions
• Points to consider before moving dectin-1 based therapeutics to clinic
• Should the use of dectin-1 agonists as anti-fungals be restricted to immunodeficiencies?
Optimizing Memory CD8+ T cell activation
Moderator: Gregoire Laveau, Ph.D., Albert Einstein College of Medicine
• Features of memory CD8+ T cells
• Subsets of innate immune cells
• PRR-dependent pathways involved
• Harnessing these mechanisms to the benefit of the host
The pros and cons of permanently and acutely transformed cells in trancripomic studies for TLR research
Moderator: Mark J. Paul-Clark, MD, Lecturer in Cardiothoracic Pharmacology,
NHLI, Imperial College London
• Has the GWAS and large quantity of omic data available in public repositories helped us to find diseases where targeting with PRR antagonists will be useful
• Will transcripomic data sets help us determine potential detrimental side effects of TLR antagonism in disease?
5:45 Reception in the Exhibit Hall with Poster Viewing
7:00 pm End of Day One