Cambridge Healthtech Institute第15回年次

Immunogenicity Prediction & Control





Registration Open12:00 pm


12:25 pm

Chairperson's Opening Remarks

Divya Pathania, PhD, Senior Scientist, AbbVie


Immune Responses to Cas9 and Emerging Cas Proteins Derived from Diverse Microorganisms

Zuben Sauna, PhD, Director, Division of Hemostasis, CBER, FDA

Immunogenicity refers to immune responses to proteins used in therapeutic applications. Immunogenicity is of concern during drug development and licensure as it can affect the safety and/or efficacy of drug products. The presentation will provide: (1) An overview of T and B cell responses to Cas9 proteins which are derived from human pathogens. (2) Compare the immune responses to Cas9 to those from novel Cas proteins which are derived from archaea and bacteriophage. Judicious application of immunogenicity risk-assessment and comparative studies of different Cas proteins could potentially help make in vivo gene editing safer.

1:00 pm

The Immunogenicity of Human-Origin Therapeutic Antibodies Is Associated with V Gene Usage

Zicheng Hu, PhD, Principal Scientist, Genentech

We performed a comprehensive analysis of 93 human or humanized therapeutic antibodies to investigate the relationship between immunogenicity risk and V/D/J gene usage. We found that V gene usage is significantly associated with clinical immunogenicity of human-origin antibodies. The result suggests that certain V genes should preferably be used in antibody engineering to reduce immunogenicity risk.

1:30 pm

Immunogenicity Risk Assessment Using In Vitro Tools and its Incorporation in Biologic Screening Funnel

Divya Pathania, PhD, Senior Scientist, AbbVie

Immunogenicity risk assessment of biotherapeutics is routinely performed through various in vitro techniques for candidate selection. In vitro assays using PBMCs can mimic protein uptake, immune cell maturation, pro-inflammatory cytokines secretion and T cell proliferation, to assess immunogenicity potential for candidate selection process. Simultaneously, critical quality attributes of formulations can be evaluated for their impact on immune response by using cell lines and human PBMC cytokine secretion assays. We have successfully developed toolbox for assessing the immunogenicity risks.

2:00 pm Unleashing the potential of MAPPS and other in vitro immunogenicity assessment tools

Sofie Pattyn, Chief Technology Officer, ImmunXperts, a Q2 Solutions Company

This presentation will showcase the use of MAPPs for assessment of unwanted immunogenicity and the importance of primary cell quality and culture conditions in combination with state-of-the-art purification of MHC complexes and ultrasensitive MS analysis of immunopeptides. Additionally, innate immune assays and T cell activation and proliferation assays will be shown.

Refreshment Break in the Exhibit Hall with Poster Viewing2:30 pm


3:10 pm

Machine Learning Approaches for Predicting and Mitigating Immunogenicity Risk

Daniel Leventhal, PhD, Head of Immunogenicity, Generate Biomedicines

Predicting the risk of unwanted immunogenicity against proteins and engineering to directly address these risks is a significant challenge when developing biotherapeutic drugs. Utilizing machine learning and computational protein design, we can tackle the complexity of this multiparameter task. Here we will review fundamental concepts involving computational prediction and mitigation of unwanted immunogenicity. We will utilize proof-of-concept examples to illustrate how we incorporate these techniques into the drug development process.

3:40 pm

Antibody Immunogenicity Risk Assessment with Graph-pMHC

Will Thrift, PhD, Senior Artificial Intelligence Scientist, Genentech

We have developed a new state of the art graph neural network model for MHC class ii peptide presentation, graph-pMHC. We show a simple strategy to accurately determine the anti-drug antibody rate of antibody drugs using the model. The work represents a step forward in accuracy for both MHC class ii peptide presentation modeling, and the prediction of immunogenicity of antibody drugs.


Assessing Immunogenicity Risks: Tools and Strategies


Divya Pathania, PhD, Senior Scientist, AbbVie


Zuben Sauna, PhD, Director, Division of Hemostasis, CBER, FDA

Zicheng Hu, PhD, Principal Scientist, Genentech

Daniel Leventhal, PhD, Head of Immunogenicity, Generate Biomedicines

Will Thrift, PhD, Senior Artificial Intelligence Scientist, Genentech

Close of Day4:40 pm

Dinner Short Course Registration5:00 pm

Recommended Dinner Short Course*5:30 pm

SC5: Advice on Putting Together an Integrated Summary of Immunogenicity
*Separate registration required. See short course page for details.



8:25 am

Chairperson's Remarks

Amy Rosenberg, MD, Senior Director of Immunology and Protein Therapeutics, Epivax

8:30 am

Overcoming Magic Bullet Approaches: Strategies for Priming the Immune System for Immune Tolerance Induction Require Multimodal Treatment

Amy Rosenberg, MD, Senior Director of Immunology and Protein Therapeutics, Epivax

Immune tolerance induction is necessary to optimize patient outcome in diverse clinical settings and treatments. In most such settings, a single magic bullet approach will be inadequate and thus, strategies to diminish extant effector mechanisms and minimize innate immune pathways will be essential to prime the immune milieu to allow induction/boosting of regulatory cells and mechanisms. This seminar will present such considerations in the context of protein, gene, and cell therapies.

9:00 am An Integrated Approach to Managing Immunogenicity Risk and Optimum Protein Design

Andrew Isidoridy, PhD, Immunology Sales Specialist, Sales, ProImmune, Inc.

Registration and Morning Coffee8:00 am


9:30 amInteractive Discussions

Interactive Discussions are informal, moderated discussions, allowing participants to exchange ideas and experiences and develop future collaborations around a focused topic. Each discussion will be led by a facilitator who keeps the discussion on track and the group engaged. To get the most out of this format, please come prepared to share examples from your work, be a part of a collective, problem-solving session, and participate in active idea sharing. Please visit the Breakout Discussions page on the conference website for a complete listing of topics and descriptions.

IN-PERSON ONLY INTERACTIVE DISCUSSION: Immunogenicity Considerations for Therapeutic Proteins used in Patients with COVID and Other Hyperinflammatory Disorders

Amy Rosenberg, MD, Senior Director of Immunology and Protein Therapeutics, Epivax

  • Effects of the inflammatory miliieu on protein structure, function and immunogenicity
  • COVID 19 hyper inflammation and induction of autoantibodies and autoimmune disease
  • Actions to consider in reassessing immunogenicity of therapeutic proteins in inflammatory contexts

IN-PERSON ONLY INTERACTIVE DISCUSSION: Advantages and Implementation of AI

Daniel Leventhal, PhD, Head of Immunogenicity, Generate Biomedicines

  • What is Artificial Intelligence and Machine Learning
  • Practical applications for use of AI tools for Immunogenicity Risk Assessment and Mitigation
  • Structuring your data to integrate with AI tools

Coffee Break in the Exhibit Hall with Poster Viewing10:20 am


11:00 am

Immunoadsorption Plasmapheresis for the Removal of Plasma Immunoglobulins to Enable Repeat Dose Administration with an AAV5 Gene Therapy Vector

Soumi Gupta, PhD, Senior Director, Head of Immunogenicity Assessment, BioMarin Pharmaceutical

The presence of pre-existing anti-AAV neutralizing antibodies (AAV NAb) may limit the efficacy of AAV-gene therapy. Moreover, a first administration of an AAV vector induces high titers of treatment emergent AAV NAb, which may compromise repeat dose administration with the same vector. Depletion of AAV NAb by immunoadsorption plasmapheresis (IAP) is a strategy that could allow successful vector administration in recipients with either pre-existing or treatment-emergent antibodies. The objective of this study was to evaluate the effectiveness of IAP to remove AAV serotype 5 (AAV5) NAb from animals sensitized by an initial gene therapy dose to enable a successful second dose administration. Results showed multiple rounds of IAP over multiple days enabled up to 99% reduction of AAV-Induced TAb titers in NHPs and enabled a successful second dose administration.

11:30 am

Differential Immune Responses to Deamidated Adeno-Associated Virus Vector

Ronit Mazor, PhD, Principal Investigator, CBER, FDA

Adeno-associated viruses (AAV) are potent vectors used for gene therapy, but recent clinical findings have revealed immunogenicity-related challenges, including formation of a cytotoxic immune response against AAV capsid protein in transfected cells. We report that deamidation, a spontaneous post-translational modification that occurs in multiple AAV serotypes, can result in formation of CD4 T cell epitopes with a Th1 cytokine pattern in donor samples with specific HLA backgrounds.

12:00 pm

Immunogenicity Prediction & Control in AAV Gene Therapy

Klaudia Kuranda, PhD, Head of Immunology, Spark Therapeutics, Inc.

Immune responses to AAV vectors are a key limitation to successful gene therapy. However, the lack of fully predictive in vitro assays and animal models has limited the speed of progress in this key area of research. The development of an end-to-end approach to immunogenicity assessment and management is critical to define an ideal vector design, manufacturing process and targeted immunosuppressive regimens.

Lunch Buffet12:30 pm


1:40 pm

Chairperson's Remarks

Susan Irvin, PhD, Senior Principal Scientist, Bioanalytical Strategy, Regeneron

1:45 pm

HESI/AAPS Reference Panel for Preclinical Immunogenicity Risk Assessment

Laurent P. Malherbe, PhD, Executive Director, Eli Lilly and Company

In vitro tools are widely used during the development of biologics to assess immunogenicity liabilities and select candidates. However, in the absence of assay standardization and harmonization, the interpretation and translation into an overall immunogenicity risk of these preclinical data remain challenging. Here we will discuss the cross-industry work led by HESI and AAPS to develop common reference biologics for immunogenicity risk assessment, a critical first step toward assay harmonization.


2:15 pm

Immunogenicity to Monoclonal Antibodies against SARS-CoV-2: Impact of Exposure and Route of Administration

Susan Irvin, PhD, Senior Principal Scientist, Bioanalytical Strategy, Regeneron

Immunogenicity is monitored at the patient level and reported at the study level, whereas aggregate program data may provide a broader understanding of humoral immunogenicity. We report data from a mAb cocktail (REGEN-COV) against the SARS-CoV-2 spike protein, across multiple studies that include a range of doses, administration routes, and durations of follow-up. We highlight the relationship between immunogenicity, exposure, and administration, as well as important implications for development of therapeutic proteins.


2:45 pm

Risk Based Approach for Development of Bioanalytical Methods to Support Clinical Immunogenicity Assessment of Multi-Domain Therapeutics

Yan Mao, PhD, Senior Principal Scientist, Boehringer Ingelheim Pharmaceuticals

This presentation will cover ADA assessment of multi-domain therapeutics with a flow chart on Boehringer Ingelheim’s risk-based approach on clinical ADA characterization of multi-domain therapeutics. Case studies of multi-domain biotherapeutics containing scFv will be provided that describe the reagents and tools used to identify the location of pre-existing ADA and domain specificity characterization in clinical ADA samples. This presentation will also share our strategy for the development of an orthogonal clinical ADA method to differentiate pre-existing ADA from treatment emergent ADA.

3:15 pm

Assessing Immunogenicity Using Immune Humanized Mice

Kristina Howard, Principal Investigator, Division of Applied Regulatory Science (DARS), CDER, FDA

3:45 pm

The Immune Epitope (IEDB) and Cancer Epitope (CEDAR) Databases; Sister Resources to Compile and Analyze Immunogenicity Data

Alessandro Sette, PhD, Professor, Vaccine Discovery & Infectious Disease, La Jolla Institute for Allergy & Immunology

We will discuss and describe the IEDB & CEDAR initiatives, which represent two sibling databases and analysis resources, focused on infectious diseases, allergy and autoimmunity epitopes, and cancer epitopes, respectively. We will start by reviewing the database structures and the epitopes derived from scientific literature and direct submissions that are hosted in the freely accessible database. Next, we will review how the data can be queried for a number of exemplary user applications. In addition, we will illustrate the various bioinformatic tools that are hosted in the databases. These tools range from tools to predict MHC binding, processing and immunogenicity, to tools to facilitate the analysis of epitope related data.

Close of Summit4:15 pm

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。


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