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:
This workstream explores the use of New Approach Methodologies (NAMs), including in vitro and in silico tools, as alternatives to animal testing for biologics. As regulatory acceptance of NAMs continues to evolve, the team is identifying scenarios where these approaches are scientifically valid and regulatory-compliant. Deliverables include generation of case studies, identification of key data gaps, and development of strategies to build regulatory confidence in NAM-based immune safety assessments. The ultimate goal is to support more ethical, efficient, and science-based approaches to evaluating biologics.
Working Group: Regulatory Strategies and Risk Assessment
This project addresses challenges in interpreting nonclinical immunotoxicity findings that are specific to a species or model system. These findings are often mischaracterized as human-relevant, leading to unnecessary delays or conservative risk management decisions. The workstream is focused on generating practical strategies to contextualize such findings using mechanistic understanding, case studies, and emerging tools like NAMs. The goal is to improve the consistency and scientific validity of regulatory assessments by distinguishing between isolated model artifacts and true indicators of human risk.
Working Group: Regulatory Strategies and Risk Assessment
This workstream is developing a weight-of-evidence approach to evaluate the carcinogenic potential of immunomodulatory compounds. It aims to integrate data sourcesâincluding clinical label information, mechanistic insights, and CRA dataâto inform hazard identification. The framework will support decisions about when additional testing (e.g., carcinogenicity studies) may or may not be needed. (Already listed on the site.)
The team is creating a practical, science-based decision tree to guide the appropriate use of cytokine release assays (CRAs) in preclinical hazard identification. This tool will help determine when CRAs are warranted based on therapeutic modality, mechanism of action, and risk context. The group is also compiling real-world case studies to illustrate best practices and limitations, aiming to foster more consistent application and interpretation of CRAs across the field.
This workstream is undertaking a retrospective analysis of preclinical immune safety data to determine its predictive value for human clinical outcomes. The project will identify correlations and disconnects between observed nonclinical findings and clinical manifestations, helping to refine how preclinical immune effects are interpreted. The team aims to produce guidance and models to support translational decision-making and risk assessment for new therapies.
The goal of this workstream is to evaluate the translational relevance of immunotoxic findings observed in non-human primates (NHPs), particularly cynomolgus monkeys. Using age-stratified models and comparative data analyses, the team will assess when NHP data are informative of human risk and when alternative models may be preferable. A weight-of-evidence (WOE) framework will be developed to guide selection of the most appropriate models for specific immuno-safety questions. This will support regulatory alignment and refinement of species selection practices.
This project supports species selection for biologics safety assessment by examining immune system similarities and differences across species. Key activities include: (1) development of a decision tree with critical considerations for species choice, including alternatives to NHPs; (2) assessment of reagent availability and operational feasibility for non-traditional models; (3) promotion of novel study designs and humanized models to improve predictive accuracy; and (4) publication of a white paper synthesizing findings and offering best practice recommendations to guide immunotoxicology studies.
This expanded commentary on the recently published  FIH Dose Selection Beyond MABEL: – continues discussions on optimizing Phase 1 clinical trial starting dose while protecting patient safety. Submission planned to Regulatory Toxicology & Pharmacology this spring. Group to sunset after publication.
This manuscript-based project focuses on differentiating true test article-related cytokine changes from natural baseline variability in cynomolgus monkeys. Drawing on retrospective data and industry experience, the team has identified key trends and messages to inform CRA interpretation. Most manuscript sections are complete, and final polishing and figure edits are underway. The findings will support improved use of CRAs in NHP models and enhance interpretation in regulatory contexts.
This ad hoc group is composed of clinical, regulatory, and scientific experts and is reactivated as needed to provide input on emerging translational challenges. It serves as a bridge between nonclinical findings and real-world clinical application, offering strategic insight that can guide ongoing workstreams or initiate new ones based on relevance to patient safety and therapeutic outcomes.
This workstream is assessing the utility of complex in vitro models (CIVMs), including organ-on-chip systems, 3D cultures, and immune-competent models, in immune safety evaluations. These models represent a promising alternative to animal studies and may enhance human relevance. The project will evaluate the current state of CIVMs, identify performance gaps, and provide guidance on effective implementation, validation considerations, and best practices to support regulatory confidence and adoption.
This project focuses on improving the reliability and standardization of immunogenicity risk assessment methods. Key activities include: (1) development of shared reagents (e.g., lyophilized monoclonal antibodies with well-characterized ADA profiles) to improve reproducibility of in vitro T-cell and innate immune assays; (2) comparative analysis of empirical methods with in silico prediction tools to define complementary strengths and limitations; and (3) collaboration with groups like AAPS to develop best practices and fit-for-purpose tools. The goal is to create a comprehensive, integrated framework for identifying and managing immunogenicity risk.
This workstream supports the development and standardization of natural killer (NK) cell functional assays used in immune safety evaluations. It aims to address challenges in assay variability, reagent selection, and interpretation. The group is working toward aligning methodologies that can be confidently applied across diverse therapeutic platforms.
This cross-functional initiative aims to enhance the visibility and impact of ITC science. Key efforts include: (1) proactive engagement with professional societies through sessions, working groups, and presentations; and (2) broad dissemination of ITC-generated knowledge via open access publications, social media campaigns, webinars, podcasts, and other communication channels. The goal is to expand awareness of immuno-safety science, drive participation, and foster collaboration across sectors.
This on-demand educational course is designed to support continuing education for scientists, regulators, and stakeholders working in immunotoxicology. Developed and delivered by ITC experts, the course covers key tools, concepts, and case examples relevant to immune safety evaluation. It is intended to strengthen scientific literacy and promote consistent application of immuno-safety principles across programs.
This manuscript, targeted for publication in the Journal of Immunology (AAI), provides a concise overview of the emerging field of immuno-safety science and its relevance at the intersection of basic and translational immunology. The piece advocates for the early and proactive integration of immune safety principles into immunology education, research design, and therapeutic development. The goal is to raise awareness within the broader immunology community and foster greater alignment between discovery science and safe clinical application.
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 menteesâ long-term goals. The second cohort will tentatively be from May â 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.
Université Paris-Saclay
Amgen, Inc.
GlaxoSmithKline
No results.
Journal of Immunotoxicology, 2010
Non-human primates (NHP), particularly macaques, are commonly used in studies conducted to assess toxicity of new pharmaceutical entities.
International Journal of Toxicology, 2008
The evolution of the subdiscipline of developmental immunotoxicology (DIT) as it exists today has been shaped by significant regulatory pressures as well as key scientific advances.
Human and Experimental Toxicology, 2002
The benefits and costs are discussed for the possibility of using pups generated in breeding studies for additional assessments, such as evaluating immunotoxicity.
Regulatory Toxicology and Pharmacology, 2014
The T-cell-dependent antibody response (TDAR) assay is a measure of immune function that is dependent upon the effectiveness of multiple immune processes, including antigen uptake and presentation, T cell help, B cell activation, and antibody production.
Human and Experimental Toxicology, 2002
Evidence is presented to demonstrate that the rat is a sensitive rodent species for developmental immunotoxicity testing of chemicals.
Human and Experimental Toxicology, 2002
There are many limitations to analyse the developing immune system in humans, thus there is need for experimental animal models to study the environmental influences during the ontogeny of the immune system.
The Immuno-Safety Technical Committee (ITC)Â is part of the Center for Translational Sciences. This HESI Center serves as a focal point for staff to share strategic approaches, scientific developments, management best practices and innovations with other related HESI committees.
Other Committees in the Center for Translational Sciences are:
For questions about the Center contact:
hesi@hesiglobal.org
Phone: +1-202-659-8404
Fax: +1-202-659-8403
740 15th Street NW, Suite 600
Washington, DC 20005
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