Immune Aspects of Biopharmaceuticals and Nanomedicines

Raj Bawa, MS, PhD, is president of Bawa Biotech LLC, a biotech/pharma consultancy and patent law firm based in Ashburn, Virginia, USA (founded in 2002). He is a registered patent agent licensed to practice before the US Patent Office, scientific advisor to Teva (Israel), visiting research scholar at the Pharmaceutical Research Institute (Rensselaer, NY), and vice president of Guanine, Inc. (Rensselaer, NY). Currently, he is principal investigator of a CDC grant to develop an assay for carbapenemase-resistant bacteria. Dr. Bawa was a primary examiner at the US Patent Office from 1996 to 2002 and an adjunct professor at Rensselaer (Troy, NY) from 1998 to 2018, where he received his PhD (biochemistry/ biophysics). He has authored over 100 publications, co-edited 4 texts, and serves as an associate editor of Nanomedicine (Elsevier). Janos Szebeni, MD, PhD, DSc, is director of the Nanomedicine Research and Education Center at Semmelweis University School of Medicine in Budapest, Hungary. He is also founder and CEO of SeroScience, Ltd. (based in Boston, Massachusetts), and a full professor of immunology and biology at the University of Miskolc in Hungary. He has made significant contributions to three fields: artificial blood, liposomes, and the complement system. His original works led to the "CARPA" concept, i.e., that complement activation underlies numerous drug-induced (pseudo) allergic (infusion) reactions.Thomas J. Webster, MS, PhD (H index: 77), is the Art Zafiropoulo Professor and department chair of Chemical Engineering at Northeastern University. He has graduated or supervised over 109 visiting faculty, clinical fellows, post-doctoral students, and thesis completing BS, MS, and PhD students. He is the founding editor-in-chief of the International Journal of Nanomedicine and a past president of the U.S. Society for Biomaterials.Gerald F. Audette, PhD, has been a faculty member at York University in Toronto, Canada, in the Department of Chemistry since 2006. Currently he is associate professor in the department and a member of the Centre for Research on Biomolecular Interactions at York University. Dr. Audette is the co-editor of volumes 1-4 of the Pan Stanford Series on Nanomedicine and is a subject editor of structural chemistry and crystallography for the journal FACETS.

• List of Corresponding Authors, Foreword, My Life with Biologicals and Nanodrugs: A Twenty-Year Affair, 1. Current Immune Aspects of Biologics and Nanodrugs: An Overview, 2. Immunological Issues with Medicines of Nano Size: The Price of Dimension Paradox, 3. Immunotherapy and Vaccines, 4. Site-Specific Antibody Conjugation for ADC and Beyond, 5. Current Understanding of Interactions between Nanoparticles and the Immune System, 6. Auto-antibodies as Biomarkers for Disease Diagnosis, 7. The Acceleated Blood Clearance Phenomenon of PEGylated Nanocarriers, 8. Anti-PEG Immunity Against PEGylated Therapeutics, 9. Complement Activation: Challenges to Nanomedicine Development, 10. Intravenous Immunoglobulin at the Borderline of Nanomedicines and Biologicals: Antithrombogenic Effect via Complement Attenuation, 11. Lessons Learned from the Porcine CARPA Model: Constant and Variable Responses to Different Nanomedicines and Administration Protocols, 12. Blood Cell Changes in Complement Activation-Related Pseudoallergy: Intertwining of Cellular and Humoral Interactions, 13. Rodent Models of Complement Activation-Related Pseudoallergy: Inducers, Symptoms, Inhibitors and Reaction Mechanisms, 14. Immune Reactions in the Delivery of RNA Interference-Based Therapeutics: Mechanisms and Opportunities, 15. Lipid Nanoparticle Induced Immunomodulatory Effects of siRNA, 16. Nanovaccines against Intracellular Pathogens Using Coxiella burnetii as a Model Organism, 17. Immunogenicity Assessment for Therapeutic Protein Products, 18. Assay Development and Validation for Immunogenicity Testing of Therapeutic Protein Products, 19. The “Sentinel”: A Conceptual Nanomedical Strategy for the Enhancement of the Human Immune System, 20. Immunotherapy for Gliomas and Other Intracranial Malignancies, 21. Engineering Nanoparticles to Overcome Barriers to Immunotherapy, 22. Metal-Based Nanoparticles and theImmune System: Activation, Inflammation, and Potential Applications, 23. Silica Nanoparticles Effects on Hemostasis, 24. Valproate-Induced Rodent Model of Autism Spectrum Disorder: Immunogenic Effects and Role of Microglia, 25. Accelerated Blood Clearance Phenomenon and Complement Activation-Related Pseudoallergy: Two Sides of the Same Coin, 26. Current and Rising Concepts in Immunotherapy: Biopharmaceuticals versus Nanomedicines, 27. Characterization of the Interaction between Nanomedicines and Biological Components: In vitro Evaluation, 28. Unwanted Immunogenicity: From Risk Assessment to Risk Management, 29. Emerging Therapeutic Potential of Nanoparticles in Pancreatic Cancer: A Systematic Review of Clinical Trials, 30. SGT-53: A Novel Nanomedicine Capable of Augmenting Cancer Immunotherapy, Index

"This outstanding volume represents a review of the various effects of biopharmaceuticals and nanomedicines on the immune system: immunotherapy, vaccines, and drug delivery; challenges and overcoming translational barriers stemming from immunotoxicity; strategies to designing more immunologically friendly formulations." —África González-Fernández, PhD, MD, Professor of Immunology and President of the Spanish Society of Immunology, University of Vigo, Spain "For those who are specialists, and for those interested in a broader understanding of biologics and nanomedicines, this is a superb book, with internationally accomplished contributors. It serves both as a reference and as a practical guide to the newest advances in these important fields. Highly recommended!"—Carl R. Alving, MD, Emeritus Senior Scientist, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA "A skillfully produced book that addresses an often-missed topic: immune aspects of biologicals and nanoscale therapeutics, with an emphasis on clinical relevance and applications." —Rajiv R. Mohan, PhD, Professor and Ruth M. Kraeuchi Missouri Endowed Chair Professor, University of Missouri, Columbia, USA"An indispensable masterpiece! It represents a rich source of information on interactions of biologics and nanodrugs with the immune system—all critical for medical applications. Volume 3, once again, achieves the series’ high standards."—László Rosivall, MD, PhD, DSc Med, Med habil., Széchenyi Prize Laureate and Professor, Faculty of Medicine, Semmelweis University, Budapest, Hungary "Hats off to Dr. Bawa for producing yet another impressive volume in terms of scope, timeliness, and relevance. With expert contributions from around the globe, this book addresses topics germane to researchers, clinicians, drug and biotherapeutic companies, regulators, policymakers, and patients." —Sara Brenner, MD, MPH, Associate Professor and Assistant Vice President, SUNY Polytechnic Institute, Albany, New York, USA"Marvelous! This timely book shows clearly that while an immune reaction to "nano-exposure" is usually unwanted, the same response also bears an immense potential." —Silke Krol, PhD, IRCCS Istituto Tumori "Giovanni Paolo II" and Fondazione IRCCS Istituto Neurologico "Carlo Besta," ItalyThe enormous advances in the immunologic aspects of biotherapeutics and nanomedicines in the past two decades has necessitated an authoritative and comprehensive reference source that can be relied upon by immunologists, biomedical researchers, clinicians, pharmaceutical companies, regulators, venture capitalists, and policy makers alike. This text provides a thorough understanding of immunology, therapeutic potential, clinical applications, adverse reactions, and approaches to overcoming immunotoxicity of biotherapeutics and nanomedicines. It also tackles critical, yet often overlooked topics such as immune aspects of nano-bio interactions, current FDA regulatory guidances, complement activation-related pseudoallergy (CARPA), advances in nanovaccines, and immunogenicity testing of protein therapeutics.