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® MISSION
® BACKGROUND
® OBJECTIVES
® COMMITTEE ACTIVITIES
® CURRENT ACTIVITIES
® COMMITTEE PARTICIPANTS
® LEADERSHIP AND INFORMATION
The mission of the Immunotoxicology Technical Committee is to identify and address scientific issues related to the development and application of immunotoxicology to public health and human health risk assessment; promote the understanding and appropriate use of immunotoxicologic data to protect human health; and contribute substantively to the scientific decision-making processes relative to the development of guidelines and regulations for immunotoxicologic testing at the local, national, and international levels.
The use of immunologic endpoints in the toxicologic assessment of drugs and chemicals has led to development of immunotoxicology as a scientific discipline. Immunotoxicology, as defined by the National Research Council, is the study of injury to, or caused by, the immune system that can result from occupational, inadvertent, or therapeutic exposure to environmental chemicals or biologic materials. The field has two broad research areas: one explores suppression of the immune response; the other examines enhanced or excessive immune response, such as occurs in allergy or autoimmunity. Chemical substances may affect the immune system, but the significance of many immunotoxic findings in animal studies is not well understood in terms of mechanism or relevance for humans. There is a need for better understanding of and improvement in the predictive value and use of current immunotoxicologic testing in animals for human health risk assessment.
The Immunotoxicology Technical Committee (ITC) was initially convened as a task force in 1990 and approved by the ILSI HESI Board of Trustees as a Technical Committee in January 1992 to address scientific issues relative to the field of immunotoxicology. As such, the ITC is the oldest component of HESI’s scientific portfolio.
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The objectives of the ITC Committee are to:
· Encourage the development and application of immunotoxicology to public health and human health risk assessment;
· Contribute to the scientific discussion of immunotoxicologic issues both nationally and internationally, and by virtue of such discussion and an emphasis on sound science, provide support for the global harmonization of immunotoxicologic testing guidelines and regulations;
· Explore and encourage opportunities to foster the exchange of information between clinical immunologists and immunotoxicologists on the relevance of immunotoxicologic findings in animals and humans and their relationship to the evaluation of human health risks;
· Support the development of scientifically adequate preclinical databases to validate immunotoxicology assessment methods and confirm the relevance of immunotoxicologic testing in animals to public health protection;
· Encourage the development of adequate clinical and epidemiologic data to understand the human response to immunosuppressive agents and their impact on public health; and
· Develop and support symposia and workshops, research projects, publications, and other initiatives to improve the science of immunotoxicology.
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· Submitted scientific comments in March 2000 to the European Agency for the Evaluation of Medicinal Products, in response to a request for comment on A Note for Guidance on Repeated Dose Toxicity, by the Committee for Proprietary Medicinal Products.
· Submitted scientific comments in December 2000 to the U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, in response to their request for comments on Draft Guidance for Industry: Considerations for Reproductive Toxicity Studies for Preventive Vaccines for Infectious Disease Indications.
· Sponsored a workshop on Developmental Immunotoxicology and Risk Assessment, with input on planning from the U.S. Environmental Protection Agency. The workshop was held on June 12-13, 2001, in Washington, DC, and addressed issues related to chemical effects on the developing immune system. Workshop proceedings were published in Human and Experimental Toxicology (Vol. 21, No. 9-10, 2002).
· The ITC organized two activities focused on respiratory hypersensitivity testing, an expert roundtable discussion in May 2003, and a full workshop in June 2004. Over seventy scientists representing academia, government and industry participated in the two-day international workshop at which chemical-, drug-, and protein specific issues associated with respiratory hypersensitivity were considered. A ‘writing team’ consisting of members of the ITC along with key government colleagues (the European Medicines Evaluation Agency [EMEA], EPA, and FDA) was identified to prepare a summary from the workshop entitled “Assessing the Potential to Induce Respiratory Hypersensitivity”. The summary of this workshop identifies the priority work related to respiratory hypersensitivity that needs to be done and has recently been accepted for publication in Toxicological Sciences.
· Sponsored a workshop on Mechanisms to Increase IDHR Research Opportunities, November 17-18, 2003, in Washington, DC. The purpose of this workshop was to identify and enhance potential mechanisms to increase research opportunities related to immune-mediated drug hypersensitivity reactions, and to determine pathways forward to implement these approaches. This workshop was a follow-up to the 2002 Task Force report on IDHR Research and resulted in a publication entitled Immune-mediated Drug Hypersensitivity Reactions (IDHR) Workshop: Mechanisms to Increase IDHR Research Opportunities which will be published in the Journal of Immunotoxicology, (Vol. 1: p. 201-205, 2005). In addition, the ITC contributed sponsorship to a Gordon conference to discuss issues of Adverse Drug Reactions, June 5-10, 2005 at Connecticut College, New London, CT.
· As a follow-up to the May 2003, roundtable on developmental immunotoxicology, a number of ITC members, working with colleagues from the U.S. Environmental Protection Agency (EPA), the U.S. Food and Drug Administration (FDA) and the National Institute for Occupational Safety and Health (NIOSH), captured key points and recommendations that were discussed. The resulting manuscript, entitled, “A Proposed Testing Framework for Developmental Immunotoxicology (DIT),” was published in Toxicological Sciences (Vol. 83: p. 18-24, 2005). The output from this effort was also featured in a poster session at the EPA science forum, May 16-18, 2005 Washington, D.C.
· The ITC co-sponsored and co-organized an ‘Immunotoxicogenomics’ workshop, September 27-28, 2005 at the Research Triangle Park campus of the Environmental Protection Agency to discuss the potential role of genomics techniques for immunotoxicity testing along with colleagues from NHEERL/EPA, NIOSH/CDC and NIEHS. The major focus of the meeting was the theoretical and practical utility of genomics techniques to replace or supplement current screening procedures, to provide insight into potential mode or mechanisms of action, and to provide data suitable for risk assessment. Immunotoxicogenomics workshop invited speakers included colleagues from government, academia and industry.
· In October 2004, the ITC hosted a roundtable discussion on “Preclinical Data for Human Immunogenicity Testing of Large Molecules.” The roundtable steering team included members of the ITC and representatives from the FDA.
· In February 2005, the ITC hosted a workshop on clinical immunotoxicity testing. Real-life examples of clinical immunotoxicity assessments were shared to facilitate discussion of how such assessments are conducted, how nonclinical data feed into such assessments, and how data from various assays are best interpreted in assessing clinical immunotoxicity.
· The committee addressed testing of a modified version of the Local Lymph Node Assay, termed the Lymph Node Proliferation Assay (LNPA). The ITC Subcommittee responsible for this activity was comprised of academic, regulatory and industry scientists. A manuscript entitled Evaluation of a Lymph Node Proliferation Assay for its Ability to Detect Pharmaceuticals with Potential to Cause Immune-Mediated Drug Reactions was published in the peer-reviewed journal Journal of Immunotoxicology (Vol. 2: p. 11-20, 2005).
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· The ITC provided comments to the European Agency for the Evaluation of Medicinal Products (EMEA) on the CHMP "Concept Paper on Guidelines on Immunogenicity Assessment of Therapeutic Proteins" in May 2006. Comments will be provided to the agency on its “Guideline on Immunogenicity Assessment of Biotechnology-derived Therapeutic Proteins” in July 2007.
· The committee is providing financial support to a research project on the Development of an Animal Model to Predict Drug-induced Allergy and Autoimmunity by Using the Oral Route of Exposure. The goal of this research, conducted in the laboratory of Dr. Raymond Pieters of Utrecht University in The Netherlands, has been to evaluate the use of a reporter antigen technique in an oral exposure model to assess the potential of pharmaceuticals to cause systemic immunosensitization in humans.
· The committee examined various assays used to detect T cell-dependent antibody responses (TDAR). The objective of this examination was to assess the robustness and validity of the various assay methods, to discuss variability of assay results, and to illustrate the sensitivity of various assay methods for the detection of immunosuppression. Results obtained using various TDAR testing protocols were analyzed by a biostatistician. The report of the committee was published in the peer-reviewed on-line journal Perspectives in Experimental and Clinical Immunotoxicology in March 2007.
· Following on the TDAR project described above, the ITC is conducting a project aimed at better characterization of the immunological responses of non-human primates (NHP). Members of the NHP project steering team developed critically important data-capture tools that allowed participating laboratories to submit results from various TDAR assay methods and flow cytometry in NHP. The data collection phase of this study is complete and statistical analysis is underway. A workshop is being contemplated. Proceedings or a project report will be submitted for publication in a peer-reviewed journal.
· Building on the foundation of the first workshop on clinical immunotoxicity testing, held in February 2005, the ITC conducted a workshop addressing both clinical immunotoxicology and immunodulators in May 2007, with some 70 participants. Proceedings from the workshop are being developed and will be submitted to a peer-reviewed journal for publication. To download presentations from this workshop, click here.
· Following on from the 2004 roundtable discussion on “Preclinical Data for Human Immunogenicity Testing of Large Molecules”, the ITC is conducted an "Immunogenicity Roundtable" as part of a joint meeting on the "Nonclinical Safety Evaluation of Biopharmaceuticals," in Lyon, France, on October 1-3, 2007. This is part of the annual “Summer School in Immunotoxicology,” which will also include an International Conference on Harmonisation session. Proceedings from the roundtable will be submitted for publication to the on-line journal Perspectives in Experimental and Clinical Immunotoxicology. To view the joint meeting program, click here.
- The ITC is addressing the issue of Photoallergy Testing to gain clarification on current testing guidelines and to discuss the preclinical testing strategies and research gaps, with input planned to a DIA workshop on photosafety in fall 2007, and possible additional activities following that workshop.
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3M Pharmaceuticals
Abbott Laboratories
Amgen, Inc.
AstraZeneca Pharmaceuticals
Bayer AG
Boehringer-Ingelheim
Bristol-Myers Squibb Company
The Dow Chemical Company
E.I. DuPont Company
Eli Lilly and Company
GlaxoSmithKline
Hoffman-La Roche AG
Johnson and Johnson – Centocor
Merck and Company, Inc.
Novartis Pharma AG
Pfizer, Inc.
The Procter & Gamble Company
sanofi-aventis.
Schering-Plough Research Institute
Syngenta CTL
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Chair............................................. Dr. Ellen Evans
Vice Chair........................... Dr. Thomas Kawabata
Scientific Advisors................. Dr. Kimber White, Jr.
Virginia Commonwealth University
Prof. dr. Hans Merk
University of Aachen
HESI Staff.................................. Mr. David Sandler
Mr. Eric Moore
For more information, please contact Mr. David Sandler at 202-659-3306, or dsandler@hesiglobal.org.
To download the Immunotoxicology Technical Committee fact sheet, click here.
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