The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform
Michael I. Luster - One of the best experts on this subject based on the ideXlab platform.
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A historical perspective of Immunotoxicology
Journal of immunotoxicology, 2013Co-Authors: Michael I. LusterAbstract:AbstractAn historical perspective of Immunotoxicology is presented beginning from early observations in which exposure to workplace environments led to unexpected immune-mediated lung diseases to its eventual evolution as a sub-discipline in toxicology. As with most toxicology disciplines, Immunotoxicology originated from concerns by scientists within industry and government as well as medical professionals to limit human exposure to agents that can potentially effect human health. The basis for these concerns originated from laboratory studies in experimental models and clinical observations that suggested certain industrial and agrochemicals, pharmaceuticals and consumer products were capable of inadvertently interacting with the immune system and cause adverse health effects. The types of immunopathologies observed and mechanisms responsible were found to be broad, being dependent upon the physiochemical properties of an agent, exposure route, and target organ/tissue, and included allergic/hypersensiti...
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Consensus Workshop on Methods to Evaluate Developmental
2013Co-Authors: Michael I. Luster, Jack H. Dean, Dori R. GermolecAbstract:17–18 October 2001 with the goal of developing a consensus document on the most appropriate experimental approaches and assays available to assess developmental immunotoxicity. The work group was composed of scientists from academia, the chemical and pharmaceutical industries, and federal agencies with expertise in developmental immunology, developmental toxicology, Immunotoxicology, and risk evaluation. This consensus document presents an overview of the major summations made by the work group. A summary of early work in the field is provided, which includes potential immunotoxic agents, followed by brief discussions of our current understanding of developmental immunology. This report concludes with the work group’s consensus of the most appropriate experimental design and tests to screen for potential developmental immunotoxic agents in experimental models, including potential limitations and data gaps. Key words: developmental Immunotoxicology, immunoteratology, Immunotoxicology methods, perinatal exposure. Environ Health Perspect 111:579–583 (2003). doi:10.1289/ehp.5860 available vi
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Immunotoxicology: fifty years of global scientific progress.
Journal of immunotoxicology, 2012Co-Authors: Susan C. Mckarns, Mitchell D. Cohen, Nancy I. Kerkvliet, Jack H. Dean, Michael B. Bonn, Jennifer Franko, Michael D. Laiosa, B. Paige Lawrence, Robert W. Luebke, Michael I. LusterAbstract:The Immunotoxicology Specialty Section of the Society of Toxicology (SOT) celebrated the 50(th) Anniversary of the SOT by constructing a poster to highlight the milestones of Immunotoxicology during that half-century period. This poster was assembled by an ad hoc committee and intertwines in words, citations, graphics, and photographs our attempts to capture a timeline reference of the development and progressive movement of Immunotoxicology across the globe. This poster was displayed during the 50(th) Annual SOT Meeting in Washington DC in March, 2011. The poster can be accessed by any Reader at the SOT Website via the link http://www.toxicology.org/AI/MEET/AM2011/posters_rcsigss.asp#imss. We dedicate this poster to all of the founders and the scientists that followed them who have made the discipline of Immunotoxicology what it is today.
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Immunotoxicology testing: past and future.
Methods in molecular biology (Clifton N.J.), 2009Co-Authors: Michael I. Luster, G. Frank GerberickAbstract:A brief historical perspective of Immunotoxicology is presented describing the early development of predictive screening tests to identify xenobiotics that may cause immunosuppression or skin sensitization. This includes a discussion of the evolution of the discipline to support a better understanding of basic -science and improvement of human risk assessment. The last section describes the need for additional validated screening tests and recent efforts to address this gap in the other areas of Immunotoxicology including food and respiratory allergy, autoimmunity and immunostimulation.
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Considerations in Estimating Social and Economic Impacts of Immunotoxic Agents
2005Co-Authors: Laura A. Blanciforti, Michael I. Luster, Epidemiology Branch Toxicology, Molecular BiologyAbstract:To make appropriate regulatory policy decisions, the potential social and eco-nomic impacts of the policy must first be established. For environmental and occu-pational agents, social and economic impacts are derived from animal toxicology and, when available, human studies that serve as the base for risk-benefit analysis (RBA). Because immune function is associated with resistance to infectious disease, developing RBA for data derived from Immunotoxicology studies will require deter-mining the changes in the frequency or severity of infectious disease resulting from an exposure. Fortunately, considerable information is readily available for identify-ing the frequency of infectious diseases in the general population and its social and economic impacts and to assist the risk assessor when conducting RBA for immuno-toxicology endpoints. The following is a brief review describing some issues in using immunotoxicity data when conducting RBA. It presents an economic methodology to determine the economic impacts of infectious diseases to society, sources where these types of information are available, and an example using a specific infectious disease, otitis media. Key Words: risk assessment, Immunotoxicology, economic impact, risk factors, immune system disorders, cost of illness
Kenneth L. Hastings - One of the best experts on this subject based on the ideXlab platform.
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Immunotoxicology: A Brief History.
Methods in molecular biology (Clifton N.J.), 2018Co-Authors: Kenneth L. HastingsAbstract:Immunotoxicological research and testing have evolved from early studies of anaphylaxis to the robust and diverse field of Immunotoxicology as we know it today. Early studies connecting immune dysfunction with exposure to exogenous agents focused on adverse reactions to immunogenic agents present in vaccines. Over time, work done by immunologists and pathologists leads to descriptions of characteristics of immunogenic agents as well as mechanisms by which anaphylaxis occurs and an understanding of the concept of immunosuppression. These myriad achievements greatly improved public health and led the field of Immunotoxicology, which addresses all aspects of adverse immunological responses following exposure to exogenous agents as well as the development of testing paradigms to understand immunological responses of designed agents such as drugs and biologics.
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Summary of a workshop on nonclinical and clinical immunotoxicity assessment of immunomodulatory drugs.
Journal of immunotoxicology, 2009Co-Authors: Joseph R. Piccotti, Herve Lebrec, Ellen W. Evans, Danuta J. Herzyk, Kenneth L. Hastings, Leigh Ann Burns-naas, Ian S. Gourley, Daniel Wierda, Thomas T. KawabataAbstract:The number of anti-inflammatory and immunomodulatory drugs being developed in the pharmaceutical industry has increased considerably in the past decade. This increase in research and development has been paralleled by questions from both regulatory agencies and industry on how best to assess decreased host resistance to infections or adverse immunostimulation caused by immunomodulatory agents such as anti-cytokine antibodies (e.g., the tumor necrosis factor-alpha inhibitors), anti-adhesion molecule antibodies (e.g., anti-alpha-4 integrin inhibitors) and immunostimulatory molecules (e.g., anti-CD28 antibodies). Although several methods have been developed for nonclinical assessment of immunotoxicity, highly publicized adverse events have brought to light significant gaps in the application of nonclinical immunotoxicity testing in assessing potential risk in humans. Confounding this problem is inconsistent application of Immunotoxicology methods for risk assessment within the scientific community, limited understanding of appropriate immunotoxicity testing strategy for immunomodulators and inconsistent testing requests by regulatory agencies. To address these concerns, The Immunotoxicology Technical Committee (ITC) of the International Life Science Institute (ILSI) Health and Environmental Sciences Institute (HESI) organized a workshop on Immunomodulators and Clinical Immunotoxicology in May 2007. The Workshop was convened to identify key gaps in nonclinical and clinical immunotoxicity testing of anti-inflammatory and immunomodulatory agents and to begin to develop consistent approaches for immunotoxicity testing and risk assessment. This paper summarizes the outcome of the HESI ITC Immunomodulators and Clinical Immunotoxicology Workshop. Topics not discussed at the Workshop were outside the scope of this report. Although more work is needed to develop consistent approaches for immunotoxicity assessment of immunomodulators, this Workshop provided the foundation for future discussion.
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A Proposed Testing Framework for Developmental Immunotoxicology (DIT)
Toxicological sciences : an official journal of the Society of Toxicology, 2004Co-Authors: Michael P. Holsapple, Kenneth L. Hastings, Leigh Ann Burns-naas, Gregory S. Ladics, Amy L. Lavin, Susan L. Makris, Yung Yang, Michael I. LusterAbstract:A group of thirty Immunotoxicology experts from the U.S. and E.U. representing government, industry, and academia met in May 2003, in Washington, D.C., to reach consensus regarding the most appropriate methods to assess developmental Immunotoxicology (DIT) for hazard identification, including under what conditions such testing might be required. The following points represent the major conclusions from this roundtable discussion: (1) the rat is the preferred model; (2) any DIT protocol should be based on immune assays already validated; (3) DIT methods should be incorporated into standard developmental and reproductive toxicity protocols to the extent possible rather than a 'stand-alone' protocol; (4) the approach to address DIT potential should be similar for chemicals and drugs, but the experimental design should be flexible and should reflect the specific questions to be answered; (5) it is possible to utilize a study design that assesses all critical windows in one protocol, with the results leading to further study of specific effects, as warranted; (6) animals should be exposed throughout the treatment protocol; (7) the triggers for DIT may include structure-activity-relationships, results from other toxicity studies, the intended use of a drug/ chemical and/or its anticipated exposure of neonates and/or juveniles.
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FORUM A Proposed Testing Framework for Developmental
2004Co-Authors: Leigh Ann Burns-naas, Kenneth L. Hastings, Gregory S. Ladics, Amy L. Lavin, Susan L. Makris, Jj Yung Yangjj, Michael I. LusterjjjAbstract:A group of thirty Immunotoxicology experts from the U.S. and E.U. representing government, industry, and academia met in May 2003, in Washington, D.C., to reach consensus regarding the most appropriate methods to assess developmental Immunotoxicology (DIT) for hazard identification, including under what conditions such testing might be required. The following points represent the major conclusions from this roundtable discussion: (1) the rat is the preferred model; (2) any DIT protocol should be based on immune assays already validated; (3) DIT methods should be incorporated into standard developmental and reproductive toxicity protocols to the extent possible rather than a ‘stand-alone ’ protocol; (4) the approach to address DIT potential should be similar for chemicals anddrugs, but the experimental design should be flexible and should reflect the specific questions to be answered; (5) it is possible toutilize a studydesign that assesses all critical windows in one protocol, wit
Jack H. Dean - One of the best experts on this subject based on the ideXlab platform.
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Consensus Workshop on Methods to Evaluate Developmental
2013Co-Authors: Michael I. Luster, Jack H. Dean, Dori R. GermolecAbstract:17–18 October 2001 with the goal of developing a consensus document on the most appropriate experimental approaches and assays available to assess developmental immunotoxicity. The work group was composed of scientists from academia, the chemical and pharmaceutical industries, and federal agencies with expertise in developmental immunology, developmental toxicology, Immunotoxicology, and risk evaluation. This consensus document presents an overview of the major summations made by the work group. A summary of early work in the field is provided, which includes potential immunotoxic agents, followed by brief discussions of our current understanding of developmental immunology. This report concludes with the work group’s consensus of the most appropriate experimental design and tests to screen for potential developmental immunotoxic agents in experimental models, including potential limitations and data gaps. Key words: developmental Immunotoxicology, immunoteratology, Immunotoxicology methods, perinatal exposure. Environ Health Perspect 111:579–583 (2003). doi:10.1289/ehp.5860 available vi
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Immunotoxicology: fifty years of global scientific progress.
Journal of immunotoxicology, 2012Co-Authors: Susan C. Mckarns, Mitchell D. Cohen, Nancy I. Kerkvliet, Jack H. Dean, Michael B. Bonn, Jennifer Franko, Michael D. Laiosa, B. Paige Lawrence, Robert W. Luebke, Michael I. LusterAbstract:The Immunotoxicology Specialty Section of the Society of Toxicology (SOT) celebrated the 50(th) Anniversary of the SOT by constructing a poster to highlight the milestones of Immunotoxicology during that half-century period. This poster was assembled by an ad hoc committee and intertwines in words, citations, graphics, and photographs our attempts to capture a timeline reference of the development and progressive movement of Immunotoxicology across the globe. This poster was displayed during the 50(th) Annual SOT Meeting in Washington DC in March, 2011. The poster can be accessed by any Reader at the SOT Website via the link http://www.toxicology.org/AI/MEET/AM2011/posters_rcsigss.asp#imss. We dedicate this poster to all of the founders and the scientists that followed them who have made the discipline of Immunotoxicology what it is today.
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Issues with introducing new Immunotoxicology methods into the safety assessment of pharmaceuticals
Toxicology, 1997Co-Authors: Jack H. DeanAbstract:Unfortunately, the principal routine toxicology methods employed for the safety assessment of new products are over 40 years old and rely primarily on histopathological evaluation. It is difficult to introduce newer Immunotoxicology or molecular toxicology methods into toxicity assessment without extensive and time consuming validation requiring several years due to concern for standardization of methods, inter-laboratory replication of these methods and resistance to acceptance of new methods by both regulatory agencies and industry. During the past 15 years, significant progress has occurred in the fields of molecular biology and basic/clinical immunology which promoted the establishment of newer more sensitive methods to assess cell injury or immune system effects in humans and laboratory animals. This brings us to the challenges associated with trying to introduce new Immunotoxicology or molecular toxicology methods into the safety assessment of new products. Our experience at Sanofi Research with immunotoxicity methods development or validation and approaches for molecular toxicology and their application to the preclinical development of new chemical drug entities (NCE) will be discussed. Laboratories to investigate immunotoxicity and molecular toxicology were established during the past 10 years among several industrial research groups for the evaluation of new chemicals and drug candidates. Immunotoxicology methods have been selected and optimized for rodent testing leading to four inter-laboratory collaborative studies to demonstrate the reproducibility and value of these methods for predicting toxicity. Our experience at Sanofi has led us to believe that these newer methods can represent an important part of drug development, should be applied on an as needed basis, and should be driven by data suggestive of an immune or molecular toxicology effect or by the class of the chemical being evaluated. Ex vivo and in vitro assays are selected from a menu of validated methods for application on a case-by-case basis. Results in this area with inter-laboratory validation of these methods will be discussed. Newer molecular toxicology and immunotoxicity methods are beginning to play a more important role in the safety evaluation and risk assessment process.
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methods in Immunotoxicology
1995Co-Authors: Gary R Burleson, Jack H. Dean, Albert E MunsonAbstract:Isolation of macrophages alveolar, peritoneal, Kupfer macrophage phagocytosis assay respiratory burst assays antigen processing and presentation assay bacterial uptake and killing by macrophages bacterial models MCMV host resistance model parasite models local lymph node assay assessment of contact photo hypersensitivity using Langerhans cell enriched epidermal cells assessment of the suppressor cell assay and its dissection assays to evaluate pulmonary hypersensitivity assessment of hypersensitivity by flow cytometry autoimmunity - animal models.
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Immunotoxicology and immunopharmacology
1994Co-Authors: Jack H. DeanAbstract:The second edition of this text has been revised and refocused to reflect the transformation of Immunotoxicology from a subdiscipline of toxicology to an independent area of research that can best be described as "environmental immunology." New chapters discuss the role of immune mediators in liver, lung, and skin toxicity, in regulating chemical- metabolizing enzymes, and in the immunosuppression produced by ultraviolet light. More emphasis is placed on the clinical consequences of immunotoxicity, as well as the interpretation of experimental data for predicting, human health risk.; The second edition is divided into three major sections: immunosuppression, autoimmunity, and hypersensitivity. This new organization of the text allows for a more thorough treatment of these phenomena, with greater attention to test methods, theoretical considerations, and clinical implications. The book includes many chapters on specific environmental agents, therapeutic drugs, biological agents, and drugs of abuse, as well as on immune-mediated toxicity in specific organ systems.
Leigh Ann Burns-naas - One of the best experts on this subject based on the ideXlab platform.
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Immunotoxicology Testing of Monoclonal Antibodies in Macaca fascicularis: From Manufacturing to Preclinical Studies
The Nonhuman Primate in Nonclinical Drug Development and Safety Assessment, 2015Co-Authors: Marie-soleil Piché, Barbara Mounho-zamora, Lynne Lesauteur, Leigh Ann Burns-naasAbstract:Many therapeutic monoclonal antibodies (mAbs) are in development for a wide array of indications. Because of the nature of the product and/or the intended pharmacology, mAbs are assessed for their potential immunomodulation, whether intended or not. Immunomodulation and Immunotoxicology (i.e., immunosuppression, immunogenicity, immunostimulation) can be related. The intended immunomodulatory effect of mAbs is the intended pharmacology for clinical efficacy. Exaggerated or prolonged pharmacological activity may, however, result in adverse immunomodulation, leading to unpredictable and unintended Immunotoxicology outcomes. Nonhuman primates (NHPs) are often considered as the most relevant species to perform preclinical studies for the testing of mAb-induced immunomodulation and immunotoxicity. This chapter focuses on regulatory considerations associated with the testing of mAbs in NHPs, the mAb product and biomanufacturing process characteristics to take into consideration for immunogenicity testing, and the preclinical study designs in adult and juvenile NHPs to monitor immunomodulation.
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Summary of a workshop on nonclinical and clinical immunotoxicity assessment of immunomodulatory drugs.
Journal of immunotoxicology, 2009Co-Authors: Joseph R. Piccotti, Herve Lebrec, Ellen W. Evans, Danuta J. Herzyk, Kenneth L. Hastings, Leigh Ann Burns-naas, Ian S. Gourley, Daniel Wierda, Thomas T. KawabataAbstract:The number of anti-inflammatory and immunomodulatory drugs being developed in the pharmaceutical industry has increased considerably in the past decade. This increase in research and development has been paralleled by questions from both regulatory agencies and industry on how best to assess decreased host resistance to infections or adverse immunostimulation caused by immunomodulatory agents such as anti-cytokine antibodies (e.g., the tumor necrosis factor-alpha inhibitors), anti-adhesion molecule antibodies (e.g., anti-alpha-4 integrin inhibitors) and immunostimulatory molecules (e.g., anti-CD28 antibodies). Although several methods have been developed for nonclinical assessment of immunotoxicity, highly publicized adverse events have brought to light significant gaps in the application of nonclinical immunotoxicity testing in assessing potential risk in humans. Confounding this problem is inconsistent application of Immunotoxicology methods for risk assessment within the scientific community, limited understanding of appropriate immunotoxicity testing strategy for immunomodulators and inconsistent testing requests by regulatory agencies. To address these concerns, The Immunotoxicology Technical Committee (ITC) of the International Life Science Institute (ILSI) Health and Environmental Sciences Institute (HESI) organized a workshop on Immunomodulators and Clinical Immunotoxicology in May 2007. The Workshop was convened to identify key gaps in nonclinical and clinical immunotoxicity testing of anti-inflammatory and immunomodulatory agents and to begin to develop consistent approaches for immunotoxicity testing and risk assessment. This paper summarizes the outcome of the HESI ITC Immunomodulators and Clinical Immunotoxicology Workshop. Topics not discussed at the Workshop were outside the scope of this report. Although more work is needed to develop consistent approaches for immunotoxicity assessment of immunomodulators, this Workshop provided the foundation for future discussion.
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A Proposed Testing Framework for Developmental Immunotoxicology (DIT)
Toxicological sciences : an official journal of the Society of Toxicology, 2004Co-Authors: Michael P. Holsapple, Kenneth L. Hastings, Leigh Ann Burns-naas, Gregory S. Ladics, Amy L. Lavin, Susan L. Makris, Yung Yang, Michael I. LusterAbstract:A group of thirty Immunotoxicology experts from the U.S. and E.U. representing government, industry, and academia met in May 2003, in Washington, D.C., to reach consensus regarding the most appropriate methods to assess developmental Immunotoxicology (DIT) for hazard identification, including under what conditions such testing might be required. The following points represent the major conclusions from this roundtable discussion: (1) the rat is the preferred model; (2) any DIT protocol should be based on immune assays already validated; (3) DIT methods should be incorporated into standard developmental and reproductive toxicity protocols to the extent possible rather than a 'stand-alone' protocol; (4) the approach to address DIT potential should be similar for chemicals and drugs, but the experimental design should be flexible and should reflect the specific questions to be answered; (5) it is possible to utilize a study design that assesses all critical windows in one protocol, with the results leading to further study of specific effects, as warranted; (6) animals should be exposed throughout the treatment protocol; (7) the triggers for DIT may include structure-activity-relationships, results from other toxicity studies, the intended use of a drug/ chemical and/or its anticipated exposure of neonates and/or juveniles.
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FORUM A Proposed Testing Framework for Developmental
2004Co-Authors: Leigh Ann Burns-naas, Kenneth L. Hastings, Gregory S. Ladics, Amy L. Lavin, Susan L. Makris, Jj Yung Yangjj, Michael I. LusterjjjAbstract:A group of thirty Immunotoxicology experts from the U.S. and E.U. representing government, industry, and academia met in May 2003, in Washington, D.C., to reach consensus regarding the most appropriate methods to assess developmental Immunotoxicology (DIT) for hazard identification, including under what conditions such testing might be required. The following points represent the major conclusions from this roundtable discussion: (1) the rat is the preferred model; (2) any DIT protocol should be based on immune assays already validated; (3) DIT methods should be incorporated into standard developmental and reproductive toxicity protocols to the extent possible rather than a ‘stand-alone ’ protocol; (4) the approach to address DIT potential should be similar for chemicals anddrugs, but the experimental design should be flexible and should reflect the specific questions to be answered; (5) it is possible toutilize a studydesign that assesses all critical windows in one protocol, wit
Herve Lebrec - One of the best experts on this subject based on the ideXlab platform.
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Immunophenotyping: Application to Safety Assessment:
Toxicologic pathology, 2017Co-Authors: Xiaoting Wang, Herve LebrecAbstract:A continuing education course entitled “What You Always Wanted to Know About Immunotoxicology in Pharmaceutical Development…But Were Afraid to Ask” was offered at the Society of Toxicologic Patholo...
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Summary of a workshop on nonclinical and clinical immunotoxicity assessment of immunomodulatory drugs.
Journal of immunotoxicology, 2009Co-Authors: Joseph R. Piccotti, Herve Lebrec, Ellen W. Evans, Danuta J. Herzyk, Kenneth L. Hastings, Leigh Ann Burns-naas, Ian S. Gourley, Daniel Wierda, Thomas T. KawabataAbstract:The number of anti-inflammatory and immunomodulatory drugs being developed in the pharmaceutical industry has increased considerably in the past decade. This increase in research and development has been paralleled by questions from both regulatory agencies and industry on how best to assess decreased host resistance to infections or adverse immunostimulation caused by immunomodulatory agents such as anti-cytokine antibodies (e.g., the tumor necrosis factor-alpha inhibitors), anti-adhesion molecule antibodies (e.g., anti-alpha-4 integrin inhibitors) and immunostimulatory molecules (e.g., anti-CD28 antibodies). Although several methods have been developed for nonclinical assessment of immunotoxicity, highly publicized adverse events have brought to light significant gaps in the application of nonclinical immunotoxicity testing in assessing potential risk in humans. Confounding this problem is inconsistent application of Immunotoxicology methods for risk assessment within the scientific community, limited understanding of appropriate immunotoxicity testing strategy for immunomodulators and inconsistent testing requests by regulatory agencies. To address these concerns, The Immunotoxicology Technical Committee (ITC) of the International Life Science Institute (ILSI) Health and Environmental Sciences Institute (HESI) organized a workshop on Immunomodulators and Clinical Immunotoxicology in May 2007. The Workshop was convened to identify key gaps in nonclinical and clinical immunotoxicity testing of anti-inflammatory and immunomodulatory agents and to begin to develop consistent approaches for immunotoxicity testing and risk assessment. This paper summarizes the outcome of the HESI ITC Immunomodulators and Clinical Immunotoxicology Workshop. Topics not discussed at the Workshop were outside the scope of this report. Although more work is needed to develop consistent approaches for immunotoxicity assessment of immunomodulators, this Workshop provided the foundation for future discussion.
