Immunotoxicology Strategies for Pharmaceutical Safety Assessment

An important reference which provides an overview of the current and recently introduced methodologies for testing the immunotoxic risks in drug candidates Helps readers understand the significance of the methods and approaches to immunotoxicology testing Aids drug scientists in industry and regulatory areas to consolidate approaches to immunotox testing Offers a definitive assessment of nonclinical models to study the toxic impacts (bio)pharmaceuticals can have on the immune system Includes chapter authors from across the pharma industry, bringing a real-world and applied perspective to immunotox testing

* An important reference which provides an overview of the current and recently introduced methodologies for testing the immunotoxic risks in drug candidates* Helps readers understand the significance of the methods and approaches to immunotoxicology testing* Aids drug scientists in industry and regulatory areas to consolidate approaches to immunotox testing* Offers a definitive assessment of nonclinical models to study the toxic impacts (bio)pharmaceuticals can have on the immune system* Includes chapter authors from across the pharma industry, bringing a real-world and applied perspective to immunotox testing

Preface ixContributors xiIntroduction to Immunotoxicology xviiJack H. DeanPart I Current Regulatory Expectations For Immunotoxicity Evaluation Of Pharmaceuticals 11 Current Regulatory Expectations for Immunotoxicity Evaluation of Pharmaceuticals 3Kenneth L. HastingsPart II Weight of Evidence Review: A New Strategy In Immunotoxicology 112.1 Clinical Pathology as Crucial Insight into Immunotoxicity Testing 13Ellen Evans2.2 Histomorphology of the Immune System: A Basic Step in Assessing Immunotoxicity 27Patrick Haley2.3 Need for Specialized Immunotoxicity Tests 45Kazuichi Nakamura2.4 Specific Drug-Induced Immunotoxicity: Immune-Mediated Hemolytic Anemia 55Raj KrishnarajPart III Nonclinical Core Immunotoxicity Testing In Drug Development 653.1.1 T Cell-Dependent Antibody Response Tests 67Joseph R. Piccotti3.1.2 Natural Killer Cell Assay and Other Innate Immunity Tests 77Lisa Plitnick3.1.3 Cellular Immune Response in Delayed-Type Hypersensitivity Test 87Karen Price3.2 Evaluation of Drug Effects on Immune Cell Phenotypes 103Laurie IciekPart IV Extended Immunotoxicology Assessment: Ex Vivo Models 1254.1 Functional Cellular Responses and Cytokine Profiles 127Elizabeth R. Gore4.2 Application of Flow Cytometry in Drug Development 141Padma Narayanan, Renold J. Capocasale, Nianyu Li, and Peter J. BugelskiPart V Extended Immunotoxicology Assessment: In Vivo Models 1615.1 Animal Models of Host Resistance 163Gary R. Burleson and Florence G. Burleson5.2 Approaches to Evaluation of Autoimmunity 179Danuta J. HerzykPart VI Immunotoxicity Testing In Biopharmaceutical Development 1896.1 Differentiation between Desired Immunomodulation and Potential Immunotoxicity 191Jeanine L. Bussiere and Barbara Mounho6.2 Relevant Immune Tests across Different Species and Surrogate Models 199Jeanine L. Bussiere6.3 Antidrug Antibody Responses in Nonclinical Studies and Their Implications 209Barbara MounhoPart VII Development of Vaccines 2177.1 Pharmacological Immunogenicity and Adverse Responses to Vaccines 219Mary Kate Hart, Mark Bolanowski, and Robert V. House7.2 Immunotoxicological Concerns for Vaccines and Adjuvants 229Catherine Kaplanski, Jose Lebron, Jayanthi Wolf, and Brian LedwithPart VIII Testing For Drug Hypersensitivity 2398.1 Systemic Hypersensitivity 241Raymond Pieters8.2 Nonclinical Models to Assess Respiratory Hypersensitivity Potential 257Curtis C. MaierPart IX Testing For Developmental Immunotoxicity 2719.1 Developmental Immunotoxicity in Rodents 273Rodney R. Dietert and Leigh Ann Burns-Naas9.2 Developmental Immunotoxicity in Nonhuman Primates 299Pauline L. Martin and Eberhard BusePart X New Methods In Assessing Immunomodulation, Immunotoxicity, and Immunogenicity 31910.1 Alternative Animal Models for Immunomodulation and Immunotoxicity 321Peter J. Bugelski10.2 Animal Models for Preclinical Comparative Immunogenicity Testing 345Daniel Wierda10.3 T Cell Epitopes and Minimization of Immunogenicity 361Harald Kropshoffer and Thomas SingerPart XI Bridging Immunotoxicology To Clinical Drug Development 37311 Bridging Immunotoxicology to Clinical Drug Development 375Ian Gourley and Jacques DescotesIndex 385