title: Summary of a workshop on nonclinical and clinical immunotoxicity assessment of immunomodulatory drugs.
abstract: 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.
authors.affiliation: Drug Safety, Schering-Plough Research Institute, Summit and Lafayette, New Jersey 07901, USA. joseph.piccotti@spcorp.com
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Piccotti
authors.forename: Herve N
authors.initials: HN
authors.lastname: Lebrec
authors.forename: Ellen
authors.initials: E
authors.lastname: Evans
authors.forename: Danuta J
authors.initials: DJ
authors.lastname: Herzyk
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Hastings
authors.forename: Leigh Ann
authors.initials: LA
authors.lastname: Burns-Naas
authors.forename: Ian S
authors.initials: IS
authors.lastname: Gourley
authors.forename: Daniel
authors.initials: D
authors.lastname: Wierda
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Kawabata
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000494:pharmacology / Q000633:toxicity; D002986:Clinical Trials as Topic / Q000592:standards / Q000639:trends*; D032921:Consensus; D003625:Data Collection; D017277:Drug Approval / Q000331:legislation & jurisprudence; D004353:Drug Evaluation, Preclinical / Q000592:standards / Q000639:trends*; D004345:Drug Industry / Q000592:standards / Q000639:trends; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000276:immunology; D007155:Immunologic Factors / Q000009:adverse effects* / Q000494:pharmacology / Q000633:toxicity; D023421:Models, Animal; D018570:Risk Assessment / Q000592:standards / Q000639:trends; D018675:Toxicity Tests / Q000592:standards / Q000639:trends*
chemical_list: D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors