The mission of the HESI Immuno-Safety Technical Committee (ITC) is to identify and address scientific issues related to immune safety and translation to human health risk assessment.
Key Objectives:
The HESI ITC seeks graduate students working in immunology, toxicology, pathology, or related field for a second cycle of their new HESI ITC Mentorship Program. This program will allow meaningful interactions between trainees and mentors to give insight on various career pathways and discuss how to streamline the mentees’ long-term goals. The second cohort will tentatively be from May – June 2023 with 4-5 one-on-one mentor meetings. As well as an opportunity to network with past mentees and expert immuno-safety committee members at our ITC annual meeting (25-26 April 2023).
If you have any questions about the HESI ITC or this program, please contact Dr. Shermaine Mitchell-Ryan
1. Ishita Choudhary, Louisiana State University
Research area: Investigating the mechanisms of ozone and allergen induce lung injury.
2. Jaclynn Meshanni, Rutgers University
Research area: The role of Lipid homeostasis in macrophages and its impact on the development of Pulmonary fibrosis resulting from Nitrogen mustard exposure.
This project aims to evaluate carcinogenicity risks associated with immunomodulators by summarizing regulatory guidance, assessing case studies, and reviewing methodologies for weight of evidence (WOE) approaches. Key objectives include:
Regulatory Review: Summarize guidance from ICH S1B, ICH S8, and the 2023 FDA Immunotoxicology recommendations.
Case Studies & Trends: Analyze existing drugs, cancer risks, and labeling while evaluating methodologies to predict cancer risk for immune modulators.
Clinical Insights: Explore tools for assessing immune status and leverage learnings from the transplant field.
Current Status: The project proposal has been finalized, case study search terms are defined, and computational toxicology reviews are underway. A publication summarizing findings is planned for 2025, with a potential workshop to further engage stakeholders under consideration.
The project team published the manuscript, “Drug Hypersensitivity Reactions: Mechanisms, Prediction, and Diagnosis,” in the Journal of Toxicological Sciences (April 2024). Originally developed as internal guidance, the manuscript was refined into a comprehensive review. It examines allergic drug hypersensitivity reactions (DHRs) associated with low-molecular-weight drugs, addressing drug- and patient-specific factors and advancements in predictive and diagnostic tools. This publication provides critical insights to inform drug safety assessments and clinical practice.
IgG Fc-containing Biotherapeutics: Translation, Pharmacological and Toxicological Effects from Animals to Humans to Support Human Risk Assessment
The project team has developed case-study-informed white paper on nonclinical safety testing approaches for characterizing the potential risks of Fc modifications engineered into antibody-based molecules. Drawing on over 20 case studies, the manuscript investigates the impact of receptor modifications on binding and activation profiles across species, focusing on Fc receptors and complement activation. This work aims to provide a comprehensive assessment of how these modifications influence nonclinical safety profiles, contributing to a deeper understanding of their implications for therapeutic development.
This collaborative project focuses on two primary goals: (1) assessing the activity and immunogenicity of reference panel antibodies across various T cell assay platforms, and (2) evaluating the impact of the freeze-drying (lyophilization) process on the activity and immunogenicity of these antibodies. The project includes 12 participating laboratories from leading pharmaceutical companies, academic institutions, and regulatory bodies.,
The study utilized two reference antibodies, (1 negative and 1positive control antibody targeting the same antigen (mimicking industry preclinical experience):
These antibodies were lyophilized at the National Institute for Biological Standards and Control (NIBSC) and distributed to participating laboratories. The data collection phase, which involved various T cell assay platforms to evaluate the antibodies’ functional activity and immunogenic potential pre- and post-lyophilization, has been successfully completed.
The team is now initiating statistical analysis to assess trends, variability, and assay performance across the datasets. Additionally, an in silico readout analysis will be conducted to compare the experimental data and provide further insights into the factors influencing antibody activity and immunogenicity. These efforts will inform the ongoing manuscript preparation, which aims to deliver standardized recommendations for antibody characterization and immunogenicity testing.
Regulatory Gaps
This group aims to provide a review of regulatory guidance documents with an educational lean to serve as a primary reference for state-of-the-art assays, models, regulatory guidance, and references.
Immunomodulation and Pregnancy Risk Assessment
This work aims to evaluate and incorporate learnings on preclinical immune safety assessment of pregnancy risk in the presence of immunomodulatory therapy. The 2020 FDA/CBER-HESI Immunomodulators and Pregnancy Risk Workshop convened key stakeholders to discuss both current and novel methodologies in preclinical and translational safety assessment of pregnancy risk associated with immunomodulatory therapy. Through the sharing of case examples, followed by longer in-depth discussion within each session, the goal was to begin to address gaps in biology, current tools, and other aspects of pregnancy risk that need to be considered during drug development. The 2020 HESI Symposium on Assessing Pregnancy Risk of Immunomodulators provided a broad overview of the role of the maternal immune system in the establishment, maintenance, and completion of a healthy pregnancy. The sessions covered both current and novel methodologies in preclinical and translational safety assessment of pregnancy risk associated with immunomodulatory therapy as well as address gaps in biology, current tools, and other aspects of pregnancy risk for consideration during drug development. An overview of marketed therapeutics highlighted current knowledge of the effects of immunomodulators on pregnancy in nonclinical animal models, potential class effects, and available data from patients exposed during pregnancy.
Nanomedicine (Nanopharmacology)
A position paper on the immunotoxicity assessment of nanomedicines is being developed.
NK/CTL Assays
The team is finalizing the manuscript, “Current Approaches to Evaluating Natural Killer (NK) Cell Function in Non-Clinical Immune Safety Assessments,” which highlights the critical role of NK cells in drug safety evaluations. Key sections include NK cell biology, current methodologies for assessing their function, advanced technologies like single-cell RNA sequencing and mass cytometry, and regulatory guidance.
This work provides practical recommendations for integrating NK cell evaluations into non-clinical safety studies, addressing gaps in current practices, and standardizing methodologies. The manuscript aims to support researchers and regulators in predicting immune-related risks, advancing the field of immunotoxicology, and improving drug safety profiles.
Examining the Use of Humanized Mice as a Preclinical Model in Drug Development
The Humanized Mouse Model project has been temporarily paused to allow the team to reassess its direction and ensure its long-term impact and relevance. While humanized mouse models hold great potential, current challenges stem from limited case studies, as these models are costly and their utility remains underexplored. Additionally, a number of recent review papers on this topic have saturated the field, underscoring the need for a novel approach to maintain scientific value and differentiation.
This project was designed to identify gaps and issues associated with the use of humanized mouse models, particularly in drug discovery and cytokine release syndrome (CRS) research, and to propose solutions through targeted projects. The group recognizes that the novelty lies in actionable insights derived from case studies, which remain a limiting factor at this time.
As we pause, the group plans to revisit this topic in the future as part of an interest group discussion, with a focus on identifying new scientific advancements and opportunities for collaboration. This strategic step ensures that when the project resumes, it will be equipped to deliver unique, impactful contributions to the field.
Cytokine-Release Assay-In Vivo Cytokine Release
This project is evaluating what parameters contribute to the variability in cyno control animals.
FIH Dose Selection for Immunomodulators
This work aims to determine a suitable course of action for establishing a first-in-human (FIH) dose for various types of immunomodulators.
Drug Hypersensitivity Reactions
This work will develop a compendium on how to assess and test for drug hypersensitivity reactions in both preclinical and clinical settings.
Immunotoxicology Training Course
The ITC convenes an annual training course on immune safety science. The training course will transition to a virtual modular format to broaden the committee’s reach and add flexibility to course offerings.
Science Outreach
These efforts aim to develop resources and activities for outreach at select scientific meetings and to create a platform to advocate and educate the next generation of immuno-safety scientists.
ITC Website Development
An ITC-centric website where both scientists and the public can find information on the field of immuno-safety has been developed. Visit the website here: https://immunosafetyresource.org/
ITC Clearinghouse Database
This work aims to create a clearinghouse/database that contains resource information related to the field of immune safety and to share information internally and externally to drive education and outreach. Visit the database here: https://immunosafetyresource.org/itc-databases/
Translational Immune Safety Clinical-Pharmacology Roundtable Series
The revamped roundtable series aims to foster cross-disciplinary dialogue, advance understanding of immune safety challenges, and support actionable strategies for improving translation and data interpretation in drug development. To achieve this, the project team is expanding the series to include perspectives from experts in clinical pharmacology and biomarker discovery, enriching discussions and broadening the scope of topics.
Université Paris-Saclay
Amgen, Inc.
GlaxoSmithKline
September 24, 2019 – September 25, 2019
Silver Spring, Maryland, USA
The goal of this workshop is to discuss the preclinical and translational safety assessment of engineered T-cell therapies. The workshop will focus on six topics, followed by an in-depth discussion.
April 9, 2019 – April 10, 2019
San Francisco, California, USA
The field of immunotoxicology is a dynamic one in which changing public health concerns, novel biomedical research advances, and innovative technological developments constantly change the landscape and the way in which work is carried out and utilized. As this field requires combined expertise in both immunology and ...
Agenda: Please find workshop agenda here.
Accommodations: Click here to find a list of nearby hotels. Please note that participants are responsible for their own transportation to and from the US FDA site.
Requirements: To gain building access, you must bring acceptable and valid government issued identification (ID).
Registration: Onsite registration is now closed. To attend the workshop virtually, please use the webinar link located below.
Webinar: Click here to join the webinar.
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The goal of this workshop is to discuss the preclinical and translational safety assessment of engineered T cell therapies. The workshop will focus on six topics, followed by an in-depth discussion:
Agenda: Please find workshop agenda here.
Accommodations: Click here to find a list of nearby hotels. Please note that participants are responsible for their own transportation to and from the US FDA site.
Requirements: To gain building access, you must bring acceptable and valid government issued identification (ID).
Registration: Onsite registration is now closed. To attend the workshop virtually, please use the webinar link located below.
Webinar: Click here to join the webinar.
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We are thrilled to announce the publication of a groundbreaking white paper by the HESI Immuno-Safety Technical Committee, now available in Clinical Pharmacology & Therapeutics.
Toxicological Sciences, 2024
This review from the HESI Immuno-Safety Committee focuses on allergic reactions induced by systemically administered low-molecular weight drugs with an emphasis on drug- and patient-specific factors that could influence the development of drug-induced hypersensitivity reactions (DHRs). Strategies for predicting ...
Journal of Immunotoxicology, 2023
An insightful review by Kamperschoer et al. that provides an overview of the various methods for assessment of Cytotoxic T Lymphocytes (CTL) function in Non-Human Primates in the context of non-clinical safety assessment of immune-modulating therapeutic agents.
Regulatory Toxicology and Pharmacology, 2021
Over the last decade, immunotherapy has established itself as an important novel approach in the treatment of cancer, resulting in a growing importance in oncology. Engineered T cell therapies, namely chimeric antigen receptor (CAR) T cells and T cell receptor (TCR) T cell therapies, are platform technologies that have enabled ...
Cytokine, 2020
Author links open overlay Immunomodulatory therapeutics such as monoclonal antibodies (mAb) carry an inherent risk of undesired immune reactions. One such risk is cytokine release syndrome (CRS), a rapid systemic inflammatory response characterized by the secretion of pro-inflammatory cytokines from immune cells. It is ...
Journal of Immunotoxicology, 2020
Nonclinical immunotoxicity evaluation is an important component of safety assessment for pharmaceuticals. One in vitro assay that can be applied in a weight of evidence assessment is the human lymphocyte activation (HuLA) assay, an antigen recall assay, similar in many respects to the in vivo T-cell-dependent ...
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