SC5: In silico and in vitro Immunogenicity Risk Assessment: Overview and Real-Life Examples
SUNDAY, August 30 | 2:30 – 5:30 PM
ABOUT THIS COURSE:
This short course will cover an overview of the in vitro and in vivo tools that are available to analyze potential immunogenicity risk of protein biologics. In the first hour we will introduce various in silico algorithms that predict
potential T cell epitopes, and get a sense of their pros and cons. In the second hour we will discuss several in vitro tools such as the MAPPS assay to identify processed and presented peptides and various T cell assay formats that are used to confirm
the presence of T cell epitopes. Together these tools can be used to help select lead candidates with reduced potential immunogenicity risk or to help deimmunize potentially high immunogenicity risk proteins. Finally, in the last hour, we will present
a literature overview of real life examples where these tools are used to confirm data that is observed in the clinic as well as examples of successful deimmunization of immunogenic proteins.
WHAT YOU WILL LEARN:
- Overview of Immunogenicity with protein biologics
- Introduction of in silico tools that predict potential T cell epitopes in your protein sequence
- Introduction of in vitro tools that are used to confirm the presence of T cell epitopes
- How these tools can be combined to help select lead candidates with reduced immunogenicity risk
- How these tools can be used to successfully deimmunize proteins with high risk for immunogenicity
- An in-depth literature overview of how these tools have been used by the pharmaceutical industry to confirm in silico and in vitro tools as well as deimmunize proteins
COURSE AGENDA:
Biologics and papers to discuss:
- Secukinumab: low clinical IMG
- Novartis Paper, Kolbinger et al: MABS, Vol8 No.3, 526-550, 2016
- Used in vitro T cell activation and MAPPS assay to show low potential of Secukinumab which had low rates of ADA in clinic
- EPO: high clinical IMG
- Novartis Paper Kammuller et al: Blood Advances, Volume 1, Number 6, 2017,
- Used in vitro T cell responses to confirm cause of increased rhEPO IMG associated with PRCA
- Factor 7a: low and high clinical IMG and deimmunization
- FDA paper Sauna et al: Science Translational Medicine, Jan 11, 2017
- Compared modified and wt rFV11a using HLA binding assays, MAPPS assay, T Cell assays
- FDA paper Sauna et al: Blood Advances, Volume 3, Number 17, 2019
- Deimmunized rFVIIa which retained increased thrombin generation but did not elicit T cell responses in PBMC
- Infliximab and Rituximab: clinical correlation with in vitro tools
- B Maillere Frontiers in Immunology 2017
- Identification of CD4 epitopes using T cell lines, MAPPS assay in healthy donors and treated patients
INSTRUCTOR BIOGRAPHY:
Daron Forman, PhD, Principal Scientist, Molecular Discovery Technologies, Bristol-Myers Squibb
Daron Forman is currently a Principle Scientist within the Discovery Biotherapeutics Department of Bristol Myers Squibb.
For the last 10 years he has helped to setup an immunogenicity risk assessment core group which utilizes in silico, in vitro and in vivo tools to help select lead drug candidates for further development. He earned dual Bachelor of Arts degrees in
Biology and Psychology at the University of Rochester and then joined the lab of Dr. Aldo Rossini at the University of Massachusetts Medical School for his PhD work investigating the effects of viral infection on stem cell transplantation tolerance.
After completing his PhD in Immunology and Virology, he joined the lab of Dr. John Iacomini at Harvard University for his post-doctoral work examining mechanisms by which T cells are rendered tolerant in mice reconstituted with retrovirally transduced
bone marrow. Prior to BMS, Daron worked at Tolerx trying to understand the mechanisms of action of humanized anti-CD3 and anti-GITR monoclonal antibodies, as well as work on identifying biomarkers for both programs.
Jad Maamary, PhD, Associate Principal Scientist, Predictive and Clinical Immunogenicity, PPDM, Merck & Co. Inc.
Jad Maamary is an Associate Principal Scientist at Merck and Co., Inc. Dr Maamary is responsible for developing
and implementing novel in silico and ex vivo platforms to assess the immunogenicity of biologics, vaccines and tumor-associated neoepitopes. His current work investigates the interplay between immunomodulation and immune receptor cross-reactivity
leading to breaking of immune tolerance. Prior to Joining Merck, Dr Maamary completed a postdoctoral fellowship at the Rockefeller University under the mentorship of Jeffrey Ravetch. He discovered a novel IgG-Fc receptor on B cells which led to the
development of an innovative vaccination regimen that took advantage of pathways involved in autoimmune diseases to enhance the efficiency immunization. Dr Maamary obtained his PhD in Molecular Virology and Immunology at the Mount Sinai School
of Medicine. Under the mentorship of Dr Peter Palese he investigated viral immune evasion and helped conceptualize and develop universal vaccines for Influenza.