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

Preface ix Contributors xi Introduction to Immunotoxicology xvii Jack H. Dean Part I Current Regulatory Expectations For Immunotoxicity Evaluation Of Pharmaceuticals 1 1 Current Regulatory Expectations for Immunotoxicity Evaluation of Pharmaceuticals 3 Kenneth L. Hastings Part II Weight of Evidence Review: A New Strategy In Immunotoxicology 11 2.1 Clinical Pathology as Crucial Insight into Immunotoxicity Testing 13 Ellen Evans 2.2 Histomorphology of the Immune System: A Basic Step in Assessing Immunotoxicity 27 Patrick Haley 2.3 Need for Specialized Immunotoxicity Tests 45 Kazuichi Nakamura 2.4 Specific Drug-Induced Immunotoxicity: Immune-Mediated Hemolytic Anemia 55 Raj Krishnaraj Part III Nonclinical Core Immunotoxicity Testing In Drug Development 65 3.1.1 T Cell-Dependent Antibody Response Tests 67 Joseph R. Piccotti 3.1.2 Natural Killer Cell Assay and Other Innate Immunity Tests 77 Lisa Plitnick 3.1.3 Cellular Immune Response in Delayed-Type Hypersensitivity Test 87 Karen Price 3.2 Evaluation of Drug Effects on Immune Cell Phenotypes 103 Laurie Iciek Part IV Extended Immunotoxicology Assessment: Ex Vivo Models 125 4.1 Functional Cellular Responses and Cytokine Profiles 127 Elizabeth R. Gore 4.2 Application of Flow Cytometry in Drug Development 141 Padma Narayanan, Renold J. Capocasale, Nianyu Li, and Peter J. Bugelski Part V Extended Immunotoxicology Assessment: In Vivo Models 161 5.1 Animal Models of Host Resistance 163 Gary R. Burleson and Florence G. Burleson 5.2 Approaches to Evaluation of Autoimmunity 179 Danuta J. Herzyk Part VI Immunotoxicity Testing In Biopharmaceutical Development 189 6.1 Differentiation between Desired Immunomodulation and Potential Immunotoxicity 191 Jeanine L. Bussiere and Barbara Mounho 6.2 Relevant Immune Tests across Different Species and Surrogate Models 199 Jeanine L. Bussiere 6.3 Antidrug Antibody Responses in Nonclinical Studies and Their Implications 209 Barbara Mounho Part VII Development of Vaccines 217 7.1 Pharmacological Immunogenicity and Adverse Responses to Vaccines 219 Mary Kate Hart, Mark Bolanowski, and Robert V. House 7.2 Immunotoxicological Concerns for Vaccines and Adjuvants 229 Catherine Kaplanski, Jose Lebron, Jayanthi Wolf, and Brian Ledwith Part VIII Testing For Drug Hypersensitivity 239 8.1 Systemic Hypersensitivity 241 Raymond Pieters 8.2 Nonclinical Models to Assess Respiratory Hypersensitivity Potential 257 Curtis C. Maier Part IX Testing For Developmental Immunotoxicity 271 9.1 Developmental Immunotoxicity in Rodents 273 Rodney R. Dietert and Leigh Ann Burns-Naas 9.2 Developmental Immunotoxicity in Nonhuman Primates 299 Pauline L. Martin and Eberhard Buse Part X New Methods In Assessing Immunomodulation, Immunotoxicity, and Immunogenicity 319 10.1 Alternative Animal Models for Immunomodulation and Immunotoxicity 321 Peter J. Bugelski 10.2 Animal Models for Preclinical Comparative Immunogenicity Testing 345 Daniel Wierda 10.3 T Cell Epitopes and Minimization of Immunogenicity 361 Harald Kropshoffer and Thomas Singer Part XI Bridging Immunotoxicology To Clinical Drug Development 373 11 Bridging Immunotoxicology to Clinical Drug Development 375 Ian Gourley and Jacques Descotes Index 385