8:50 am Chair’s Opening Remarks
Reviewing the State of Play of Antigen-Specific Immunotherapies
9:00 am SWOT Analysis-Style Panel Discussion – Topics to be Addressed:
Synopsis
- What have we learnt from recent industry developments?
- What are the implications for R&D and the wider industry?
- What are the strengths and differentiators of antigen-specific immunotherapies compared to other approaches?
- What is the market opportunity and untapped clinical areas/unmet patient clinical need that holds most promise when it comes to antigen-specific immune tolerance inducing-therapies?
- How have competing drug modalities reached late-stage clinical testing and what are the bottlenecks holding back the antigen-specific immune tolerance space back from clinical success?
Characterizing Driver Antigens of Disease & Mechanisms Underlying Immune Tolerance to Drive Antigen & Epitope Discovery
9:30 am Manipulation of TGF-β for Antigen-Specific Immunotherapy of Autoimmune Diseases
Synopsis
- Explore how the development of antigen-specific T-cell therapy in animals with established autoimmunity to treat the disease is challenging and hopeful for therapy of patients with autoimmune diseases
- By manipulation of apoptosis, phagocytosis and TGF-β production in vivo, we have successfully developed an approach to autoantigen-specific Tregs in mice with established autoimmune diseases
- These in vivo generated antigen-specific Tregs potently suppress inflammation in the target organs, without compromising immunity to cancer and infection
10:00 am Inducing Tolerance to ApoB Epitopes to Curb Atherosclerosis
Synopsis
- Demonstrating that atherosclerosis is always accompanied by an autoimmune response to ApoB
- Understand that ApoB contains hundreds of HLA-restricted T cell epitopes
- Realizing that some ApoB epitopes are immunodominant
10:30 am Virtual Speed Networking & Break
11:30 am Strategies for Epitope-Based Tolerance-Inducing Immunotherapy
Synopsis
- Assess how soluble antigen arrays enhance the delivery and tolerogenicity of peptides
- The way peptides are grafted onto macromolecules has a significant impact on the safety and efficacy of therapy
- Learn how endotope constructs provide optimized and customizable solutions for epitope delivery via DNA- and mRNA-based vaccines
12:00 pm Understanding the Mechanism of Action of Imotopes™ at Molecular and Cellular Level
Synopsis
- Demonstrating proximal T-cell receptor signalling upon cognate interaction with Imotopes™-pulsed antigen-presenting cells
- Presenting single cell transcriptomics and proteomics of Imotope™-induced cytolytic CD4 T-cells Immunodeletion as a way to restore tolerance
12:29 pm
Discussing Collaborative Investment Opportunities for Industry & Academia to Engage in to Advance Immune Tolerance Drug Development Efforts
12:30 pm NIAID Funding Mechanisms for Immune Tolerance Research
Synopsis
- NIAID has a longstanding interest in immune tolerance spanning research on
basic mechanisms through clinical trials - Overview of NIAID grant and contract mechanisms suitable for individuals and
small companies - Opportunities for partnerships and collaborations
1:00 pm Lunch Networking Break
Leveraging Immune Biomarkers & Exploring Immune Tolerance in Diabetes
2:00 pm The Struggles with Immune Biomarkers and Pathologic Endotypes in Type 1 Diabetes
Synopsis
- Immune biomarkers exhibit substantial longitudinal variation in humans, they have so far failed to predict individual trajectories
- Pathologically in the human pancreas there is little evidence for completely different endotypes/pathways comparing individuals
- We have, to date, no reliable marker for antigenic tolerance that correlate reliably with clinical endpoints – learning across diseases will be needed
2:30 pm Requirement for Induced Tregs and Tr1 Cells or Regulation of Autoimmune Disease Using Antigen Encapsulating PLG Nanoparticles
Synopsis
- Ag-encapsulating biodegradable PLG nanoparticles (Ag-PLG) induce activation of Tr1 and iTreg cells which are required for tolerance induction and maintenance and dependent on IL-10
- Ag-PLG can be loaded with recombinant protein to target multiple CD4 and CD8 epitopes simultaneously
- Ag-PLG therapy has been shown to be effective for inducing tolerance to gluten challenge in celiac disease patients in Phase 1/2a clinical trial
3:00 pm Afternoon Networking Break
3:30 pm Antigen-Specific Tolerance to Multiple Epitopes in T1D
Synopsis
- Discussing how antigen-specific tolerance to multiple proteins stops progression to overt diabetes in the NOD model
- Tolerance induction by CNP-T1D included upregulation Tregs and TR1 cell populations, which resulted in inhibition of activation of diabetogenic epitopes not encapsulated within CNP
- The CNP-T1D induced tolerance was durable to the end of the study and also
prevented infiltration into the islets
4:00 pm Precision Medicine and Antigens – The Case of HLA and GADSpecific Immunotherapy in Type 1 Diabetes
Synopsis
- Retrospective and prospective clinical data show that individuals carrying HLA variants associated with autoimmunity against GAD (glutamic acid decarboxylase) respond to GAD-specific immunotherapy, supporting the notion of precision medicine in Type 1 Diabetes
- By prescreening for the presence of HLA DR3-DQ2, the HLA haplotype associated with GAD-specific autoimmunity, individuals that have a high likelihood of responding to GAD-specific immunotherapy can be selected for clinical trials
- The importance of HLA for immunity and antigen presentation provides a rational platform to develop antigen-specific therapies for heterogeneous diseases