Cambridge Healthtech Institute’s 12th Annual

Immunogenicity Prediction & Control

Regulatory Perspectives, Risk Factors, and Management

October 21 - 22, 2021 ALL TIMES EDT

The impact of immunogenicity on safety and efficacy, and consequent cost to the industry, is well understood. Accordingly, investigators are focusing on factors that contribute to immunogenicity, as well as a number of different approaches to predict immunogenicity at the drug discovery stage. There are several major problematic areas with novel modalities. Efforts are being made to suppress immune responses to these products and to introduce tolerizing and deimmunization approaches. Attend in 2021 to hear insightful feedback from the FDA and learn from top industry and academics in this field.

Thursday, October 21

12:00 pm Registration


12:45 pm

Chairperson's Opening Remarks

Marisa Joubert, PhD, Scientific Director and Group Leader, Amgen

Predicting Immune Responses to Therapeutic Proteins: The Promise of Safer Drugs and Improved Clinical Outcomes

Zuben Sauna, PhD, Research Biologist, CBER, FDA

Immunogenicity (immune responses to protein-therapeutics) is an impediment to development and licensure of therapeutic-proteins. Progress in the development and use of non-clinical assessments of immunogenicity allow science-based assessments of immunogenicity-risk.  I will illustrate how judicious application of tools available for immunogenicity risk-assessment can permit better decision-making during drug-development and licensure. Extant and emerging technologies allow for a personalized approach to immunogenicity assessment and can also be used in de-immunization strategies.

1:20 pm

The Routinization of MAPPs Enables the Precise Sequences Presented for T Cell Surveillance to Inform Immunogenicity Prediction Models

Robert Siegel, PhD, Research Fellow, Laboratory for Experimental Medicine, Eli Lilly and Company

MHC-associated peptide proteomics (MAPPs) allows the sequences presented for immune surveillance after natural processing in antigen presenting cells to be precisely defined. Throughput concerns limit implementation at the candidate or later stages of molecule development. This presentation highlights the integration of MAPPs data, along with APC internalization and a large human antibody sequence database, for the construction of a statistical model to predict the incidence of immunogenicity in early development.

Bernard Maillere, PhD, Research Director, Immunology, CEA

Mutations with respect to the germline sequences of human antibodies have been shown to drive immunogenicity, but strikingly many proteins are immunogenic even though their sequences are entirely human. Human sequences can be artificially modified by chemical modifications but there is no indication on their immunogenicity. This talk will highlight the immunological mechanisms involved in these responses in order to anticipate immunogenicity issues.



Immunogenicity of Adeno-Associated Virus (AAV) Vectors in Gene Therapy

Ronit Mazor, PhD, Principal Investigator, CBER, FDA

Adeno-associated viruses (AAV) are potent vectors used for gene delivery in gene therapy products. Recent clinical findings revealed immunogenicity-related challenges, including pre-existing antibodies, formation of neutralizing antibodies after the first administration, innate activation, and formation of a cytotoxic immune response against transfected cells. In this talk, I will provide a review of current state-of-the art of immunogenicity of AAV vectors and strategies for mitigating it.   

2:50 pm Exhibit Hall with Poster Viewing
3:30 pm

Predicting and Mitigating the Immunogenicity of Cell & Gene Therapies

Laura Salazar-Fontana, PhD, Co-Founder, Immunogenicity Integrated

Cell & Gene Therapy products are designed to modify the expression of defective genes and/or to alter the biological properties of cells and/or tissues to treat rare conditions. Changing the biological characteristics of cells is expected to elicit immune responses in the host that can compromise the safety (e.g. GVHD) and/or block the efficacity of the therapeutic product (e.g. pre-existing anti-AAV antibodies). This presentation will focus on how to identify the immunogenicity risk factors (product-intrinsic, systems biology, conditions of use, patient-related and product quality) to define the best immunogenicity testing and mitigation strategies for CGT product development.

3:55 pm

Immunogenicity Risk Assessment Methods for Novel Modalities: Adapting our Toolbox for Complex Therapeutics

Jochem Gokemeijer, PhD, Associate Director, Molecular Discovery Technologies, Bristol-Myers Squibb

Novel modalities biologics such as CAR T and gene therapy have shown remarkable clinical efficacy and are in development for multiple indications. The complexity of these modalities, as well as the multiple ways they can interact with the human immune system, can make preclinical immunogenicity risk assessment and mitigation challenging. Immunogenicity risk assessment tools developed for biologics (mAbs) can be adapted to evaluate and assess immunogenicity risk of novel modalities biologics.

4:20 pm

Developing a Risk-Based Bioanalytical Strategy for Gene-Based Therapies

Vibha Jawa, PhD, Executive Director, Bristol-Myers Squibb

Gene therapies and cellular therapies use viral vectors as vehicles to deliver gene of interest. There is an immunogenicity risk associated with such vectors as they activate the innate phase (pattern recognition receptors, complement system etc.) and prime and activate the adaptive phase response (mediated by T cells). Based on the nature of transgene and tropism of vector serotype, the risk-based bioanalytical would need to adapt to decide whether humoral or cellular immune response would be needed. 

4:40 pm

In vitro T Cell Activation Assay to Predict Immunogenicity of Biotherapeutic Products

Sivan Cohen, PhD, Scientist, Genentech

The development of anti-drug antibodies (ADAs) is an undesirable potential outcome of the administration of biotherapeutics. We have developed a novel method that provides a rapid and simple preclinical test of the immunogenic potential of a new candidate biotherapeutic or biosimilar. Implementation of this approach during biotherapeutic research and development enables rapid elimination of candidates that are likely to cause ADA-related adverse events and detrimental consequences.

5:15 pm Recommended Evening Short Course*
5:15 pm SC6: Strategic Bioassay Design

*Separate registration required. See short course page for details. 

Friday, October 22

7:30 am Registration and Morning Coffee


7:55 am

Chairperson's Remarks

Ronit Mazor, PhD, Principal Investigator, CBER, FDA

Assessing the Immunogenicity Risk of Impurities

Daniela Verthelyi, MD, PhD, Chief, Laboratory of Immunology, CDER, FDA

Multiple product and process related impurities capable of activating innate immune receptors can modify the immunogenicity risk of peptides and proteins, thus assays that assess innate immune activation by drug products can contribute to their immunogenicity risk assessment. This talk will discuss the risk posed by innate immune response modulating impurities, available assays, technical parameters and data interpretation.


Immunomodulatory Properties of the IgG Fc Domain: Benefits, Risks and Implications for Immunogenicity Assessments

Daniel LaGasse, PhD, Research Regulator, CBER, FDA
Noel Smith, PhD, Head Immunology, Early Development Services, Biologics, Lonza

Understanding potential immunogenicity risks of your therapeutic candidate is a key part of pre-clinical development. Here we discuss how a panel of healthy donors can be pre-qualified for specific assays and how this donor panel can be used in studies to assess the immunogenicity risk of therapeutics.


9:30 am Interactive 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. For in-person events, the facilitator will lead from the front of the room while attendees remain seated to promote social distancing. For virtual attendees, the format will be in a Zoom room. 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 Interactive Discussion page for a complete listing of topics and descriptions.

VIRTUAL INTERACTIVE DISCUSSION: Immunogenicity Issues with Novel Modalities: Gene Therapy, Cellular Therapies and Oligonucleotides

Ronit Mazor, PhD, Principal Investigator, CBER, FDA
  • Immune monitoring of gene therapy products (Nab vs. Tab or both) and correlates to clinical relevance
  • Cellular and humoral immunity in CAR T products
  • Impact of post translational modifications on accuracy of immune monitoring
  • Adaptive and innate immunogenicity response to oligonucleotides (e.g.; mRNA, microRNA, siRNA, ASOs)?

IN-PERSON INTERACTIVE DISCUSSION: Immune Tolerance: Immunosuppression, Tolerance Induction

Theresa Goletz, PhD, Executive Director, Theresa Goletz Consulting
  • How immune modulation impacts the imperfect balance of immune tolerance
  • Determinants of biotherapeutic antigenicity: role of antigen presenting cells
  • Role of Inflammatory Microenvironment in immunogenicity​
10:10 am Exhibit & Last Chance for Poster Viewing


11:00 am

Evaluating Immunogenicity Risk and Mitigation Strategies for Enzyme Replacement Therapy

Sue Richards, PhD, FAAPS, VP, Translational Medicine and Early Development, Sanofi

Enzyme replacement therapy (ERT) is effective in treating patients with lysosomal storage diseases. These diseases are a result of deficiency in endogenous enzyme activity, which vary in severity, and present unique considerations for immunogenicity of ERTs. Immune responses can widely vary and present challenges to predict which patients will develop a robust immune response. Approaches to identify patients and an overview of immunogenicity mitigation strategies will be discussed.

11:30 am

Key Considerations for the Preclinical Immunogenicity Risk Assessment of Biologics

Laurent P. Malherbe, PhD, Research Advisor, Eli Lilly & Co.

Predictive tools measuring specific steps of the immune response are used during drug development to decrease the risk of clinical immunogenicity. To assess the performance and help with the interpretation of these tools, control biologics with known rates of clinical immunogenicity are essential. This presentation will use a panel of control biologics to illustrate how preclinical tools could be leveraged to formulate a comprehensive strategy to assess the immunogenicity risk.

12:00 pm

A Case Study of Immunogenicity Assessment Using CD4 T Cell Activation Assays

Karen Liao, MD, Principle Scientist, Merck

In vitro CD4 T cell stimulation has been used as an indicator of immunogenicity risk for biologics. The commonly used in vitro CD4 T cell assays include dendritic cell - autologous CD4 T cell co-culture (DC-T) assay and whole PBMC assay. Here, we report the immunogenicity risk test results using both DC-T and whole PBMC assay for a monoclonal antibody which elicited strong ADA response in a Phase I study.

1:00 pm Enjoy Lunch on Your Own
2:15 pm

Chairperson's Remarks

Theresa Goletz, PhD, Executive Director, Theresa Goletz Consulting

Risk Management and the Impact of COVID-19

Panel Moderator:
Theresa Goletz, PhD, Executive Director, Theresa Goletz Consulting
João A Pedras-Vasconcelos, PhD, Biotech Quality and Immunogenicity Reviewer, Biotechnology Products, CDER, FDA
Sue Richards, PhD, FAAPS, VP, Translational Medicine and Early Development, Sanofi
Karen Liao, MD, Principle Scientist, Merck


2:50 pm

Specific Immune Tolerance for Facilitating Autoimmune Disease Therapy: Clinical Experience and Future Perspectives

Stephen Miller, PhD, Professor of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University

The utility of tolerance induction using biodegradable antigen-encapsulating carboxylated poly(lactide-co-glycolide) (PLG) nanoparticles (Ag-PLG) as a ‘negative vaccine’ for in treatment of autoimmune diseases will be discussed. The mechanisms underlying Ag-PLG tolerance induction and maintenance via activation of induced Tregs (iTregs) and Tr1 cells for controlling Th1/17-driven animal models of MS and T1D will be presented. Lastly, the safety and efficacy of tolerance using gliadin-encapsulating PLG nanoparticles for prevention of gliadin-specific T cell responses and intestinal pathology in celiac disease patients undergoing gluten challenge will be summarized. 

3:20 pm

Immunogenicity in T Cell Auto-Reactivity

Laura Santambrogio, PhD, Professor, Associate Director, Precision Immunology, Weill Cornell Medicine

The presentation will delve into the biochemical and immunological mechanisms associated with increased adjuvanticity and immunogenicity, as observed in chronic inflammatory conditions. Conditions associated with low-grade chronic inflammation sustain a tissue environment enriched in DAMP, pro-inflammatory cytokines and TLR-s-signaling molecules, which increase dendritic cell adjuvanticity. In unison, changes in the MHC II presented immunopeptidome, sustain an auto-reactive T and B cell repertoire which worsen tissue damage and immunological cell death.


Timothy Hickling, PhD, Head of Immunosafety, Roche
4:20 pm Close of Summit