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E-raamat: Immune Aspects of Biopharmaceuticals and Nanomedicines

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The enormous advances in the immunology of biotherapeutics and nanomedicines in the past two decades have necessitated an authoritative and comprehensive reference that can be relied upon by immunologists, biomedical researchers, physicians, pharmaceutical and formulation scientists, clinicians, regulatory personnel, technology transfer officers, venture capitalists, and policy makers alike. This book provides a broad survey of various interconnected topics, all accomplished in a user-friendly format. The chapters are devoted to the immune stimulatory and suppressive effects of antibodies, peptides and other biopharmaceuticals, drug carrier liposomes, micelles, polymers, polymeric vesicles, dendrimers, carbon nanotubes, and other nanomedicines (with and without surface targeting ligands). The text discusses the state of the art in nanoparticle-formulated therapeutic and preventive vaccines along with their potential molecular mechanisms underlying immunogenicity. The latter phenomenon is addressed as an adverse effect of monoclonal antibody–based biopharmaceuticals and nanomedicines. Yet another adverse immune effect of monoclonals and nanomedicines, complement activation-related pseudoallergy (CARPA), is discussed in unprecedented detail in terms of occurrence, prediction, prevention, and mechanism. The range of the contributing authors accurately reflects the diverse and rapidly evolving fields of biotherapeutics, nanomedicines, nanoimmunology, and nanotoxicology. The book’s multidisciplinary and in-depth approach makes it a standard reference in this expansive and interdisciplinary field.

Arvustused

"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 systemall 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," Italy The 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.

List of Corresponding Authors xxvii
Foreword xxix
Howard E. Gendelman
My Life with Biologicals and Nanodrugs: A Twenty-Year Affair xxxvii
Raj Bawa
1 Current Immune Aspects of Biologics and Nanodrugs: An Overview 1(82)
Raj Bawa
1.1 Introduction
3(18)
1.2 Biologics versus Small-Molecule Drugs
21(3)
1.3 What Are Nanodrugs?
24(8)
1.4 Are Biologics and Nanodrugs Adversely Immunogenic?
32(19)
1.5 Immunogenicity Assessment of Biologics and Nanodrugs
51(5)
1.6 Entering the Era of Biosimilars
56(6)
1.7 Immune Aspects of Biosimilars and Nanosimilars: The Copaxone® Example
62(5)
1.8 Concluding Remarks and Future Directions
67(16)
2 Immunological Issues with Medicines of Nano Size: The Price of Dimension Paradox 83(40)
Janos Szebeni
Raj Bawa
2.1 Adverse Immune Effects of Nanodrugs
84(10)
2.2 Issues of Terminology
94(2)
2.3 Adverse Immune Effects of Nanodrugs: The Dimension Paradox
96(15)
2.4 Vicious Cycle between Specific and Nonspecific Immune Responses to Nanodrugs
111(1)
2.5 CARPA as Blood Stress
112(2)
2.6 CARPA Testing
114(9)
3 Immunotherapy and Vaccines 123(32)
Johanna Poecheim
Gerrit Borchard
3.1 Introduction
123(1)
3.2 The Immune System
124(4)
3.3 Nanotechnology in Vaccines
128(17)
3.4 Conclusions
145(10)
4 Site-Specific Antibody Conjugation for ADC and Beyond 155(28)
Qun Zhou
4.1 Introduction
155(4)
4.2 Site-Specific ADC through Specific Amino Acids
159(2)
4.3 Site-Specific ADC through Unnatural Amino Acids
161(3)
4.4 Site-Specific ADC through Glycans
164(1)
4.5 Site-Specific ADC through Short Peptide Tags
165(1)
4.6 Site-Specific Antibody Conjugation for Diagnosis
166(3)
4.7 Site-Specific Antibody Conjugation for Other Therapeutic Applications
169(4)
4.8 Conclusions
173(10)
5 Current Understanding of Interactions between Nanoparticles and the Immune System 183(46)
Marina A. Dobrovolskaia
Michael Shurin
Anna A. Shvedova
5.1 Introduction
184(4)
5.2 Achievements
188(11)
5.3 Disappointments
199(5)
5.4 Lessons Learned
204(4)
5.5 Conclusions
208(21)
6 Auto-antibodies as Biomarkers for Disease Diagnosis 229(20)
Angelika Lueking
Heike Gohler
Peter Schulz-Knappe
6.1 Introduction
229(1)
6.2 Auto-antibodies as Biomarkers
230(3)
6.3 Auto-antibodies for Companion Diagnostics Enabling Personalized Medicine
233(2)
6.4 Biomarker Discovery Strategies
235(4)
6.5 Antigen/Auto-antibody Interactions as Biomarker Candidates
239(3)
6.6 Diagnostic Assays Based on Antigen/Auto-antibody Interactions
242(1)
6.7 Conclusion
243(6)
7 The Acceleated Blood Clearance Phenomenon of PEGylated Nanocarriers 249(40)
Amr S. Abu Lila
Tatsuhiro Ishida
7.1 Introduction
249(2)
7.2 Mechanism of ABC Phenomenon
251(3)
7.3 Correlation Between Complement Activation and ABC Phenomenon
254(2)
7.4 Factors That Affect the Magnitude of the ABC Phenomenon
256(14)
7.5 Strategies to Abrogate/Attenuate Induction of the ABC Phenomenon
270(5)
7.6 Clinical Implications of ABC Phenomenon
275(1)
7.7 Conclusion
276(13)
8 Anti-PEG Immunity Against PEGylated Therapeutics 289(22)
Amr S. Abu Lila
Tatsuhiro lshida
8.1 Introduction
289(1)
8.2 PEG Immunogenicity in Animal Models
290(3)
8.3 PEG lmmunogenicity in Humans
293(5)
8.4 Properties of Anti-PEG Antibody Epitope
298(1)
8.5 Strategies to Avert Anti-PEG Antibody Responses
299(2)
8.6 Conclusion
301(10)
9 Complement Activation: Challenges to Nanomedicine Development 311(30)
Dennis E. Hourcade
Christine T.N. Pham
Gregory M. Lanza
9.1 Introduction
311(1)
9.2 C Activation Pathways and Downstream Effectors
312(2)
9.3 Role of C in Human Health and Disease
314(2)
9.4 Complement Activation by Biomaterials
316(1)
9.5 Nanomedicine-Mediated C Activation
317(2)
9.6 Current Methods to Measure Nanomedicine-Mediated C Activation
319(9)
9.7 Conclusions
328(13)
10 Intravenous Immunoglobulin at the Borderline of Nanomedicines and Biologicals: Antithrombogenic Effect via Complement Attenuation 341(20)
Milan Basta
10.1 Introduction
341(2)
10.2 Atherosclerosis
343(4)
10.3 Antiphospholipid Syndrome
347(4)
10.4 Sickle Cell Disease
351(2)
10.5 Mechanism of IVIG Modulation of Vaso-Occlusive Disorders
353(2)
10.6 Summary and Outlook
355(6)
11 Lessons Learned from the Porcine CARPA Model: Constant and Variable Responses to Different Nanomedicines and Administration Protocols 361(28)
Rudolf Urbanics
Peter Bedocs
Janos Szebeni
11.1 Introduction: CARPA as an Immune-Mediated Stress Reaction in Blood Triggered by Nanomedicines
361(2)
11.2 In vitro Tests for CARPA
363(1)
11.3 Animal Models of Immune Toxicity: Which Is Good for CARPA Evaluation?
363(1)
11.4 Non-Standard Immunotoxicity Tests of CARPA in Different Animals
364(2)
11.5 The Use of Pigs as Disease Models
366(1)
11.6 Technical Details of the Porcine CARPA Model
366(1)
11.7 The Symptom Tetrad
367(2)
11.8 Uniqueness of the Porcine CARPA Model
369(1)
11.9 Invariable Parameters of Porcine CARPA
369(2)
11.10 Variable Parameters of Porcine CARPA
371(5)
11.11 Summary and Future Directions
376(13)
12 Blood Cell Changes in Complement Activation-Related Pseudoallergy: Intertwining of Cellular and Humoral Interactions 389(28)
Zsofia Patko
Janos Szebeni
12.1 Introduction
389(1)
12.2 Blood Cell Changes in CARPA: Human and Animal Data
390(3)
12.3 Platelets and Their Role in CARPA
393(6)
12.4 Zooming on Interactions, Receptors and Mediators in CARPA-Associated Blood Cell Changes
399(8)
12.5 Conclusions
407(10)
13 Rodent Models of Complement Activation-Related Pseudoallergy: Inducers, Symptoms, Inhibitors and Reaction Mechanisms 417(24)
Laszlo Dersi
Laszlo Rosivall
Peter Hamar
Janos Szebeni
Gabor Szenasi
13.1 Introduction
417(1)
13.2 The CARPA genic Effects of CVF, Zymosan and LPS in Rodents and Their Modulation with Complement Antagonists
418(2)
13.3 CARPA in Pregnancy
420(1)
13.4 Characteristics of Liposome-Induced CARPA in Rats
420(6)
13.5 Effects of Complement Components C3a and C5a in the Guinea Pig
426(2)
13.6 Effects of Complement Components C3a and C5a in the Rat
428(1)
13.7 Effects of Complement Components C3a and C5a in the Rabbit, Hamster and Mouse
429(2)
13.8 Conclusions
431(10)
14 Immune Reactions in the Delivery of RNA Interference-Based Therapeutics: Mechanisms and Opportunities 441(32)
Kaushik Thanki
Emily Falkenberg
Monique Gangloff
Camilla Foged
14.1 Background
441(4)
14.2 Overview of Approaches for Efficient Intracellular Delivery of siRNA
445(7)
14.3 Immune Reactions Elicited during RNAi Therapy
452(4)
14.4 Recent Advancements in Predicting Immunological Complications
456(6)
14.5 Conclusions and Future Perspectives
462(11)
15 Lipid Nanoparticle Induced Immunomodulatory Effects of siRNA 473(34)
Ranjita Shegokar
Prabhat Mishra
15.1 Introduction
473(1)
15.2 Discovery of siRNA
474(3)
15.3 Strategies for Delivering siRNA
477(2)
15.4 Immune Response to siRNA Payload and Its Modulation
479(12)
15.5 Clinical Status
491(3)
15.6 Conclusions
494(13)
16 Nanovaccines against Intracellular Pathogens Using Coxiella burnetii as a Model Organism 507(30)
Erin J. van Schaik
Anthony E. Gregory
Gerald F. Audette
James E. Samuel
16.1 Introduction
507(1)
16.2 Using Nanomedicine to Tackle Intracellular Pathogens
508(1)
16.3 C. burnetii Bacteriology
509(1)
16.4 Epidemiology and Clinical Manifestations
509(1)
16.5 Virulence
510(2)
16.6 Immune Evasion Strategies
512(2)
16.7 Qvax® and Correlates of Protective Immunity
514(2)
16.8 Nanovaccines
516(6)
16.9 Why Are Nanoparticle Vaccines a Good Strategy for C. burnetii?
522(15)
17 Immunogenicity Assessment for Therapeutic Protein Products 537(48)
17.1 Introduction
538(1)
17.2 Background
539(1)
17.3 Clinical Consequences
540(5)
17.4 Recommendations for Immunogenicity Risk Mitigation in the Clinical Phase of Development of Therapeutic Protein Products
545(4)
17.5 Patient-and Product-Specific Factors That Affect Immunogenicity
549(18)
17.6 Conclusion
567(18)
18 Assay Development and Validation for Immunogenicity Testing of Therapeutic Protein Products 585(42)
18.1 Introduction
586(1)
18.2 Background
587(1)
18.3 General Principles
588(3)
18.4 Assay Design Elements
591(17)
18.5 Assay Development
608(7)
18.6 Assay Validation
615(6)
18.7 Implementation of Assay Testing
621(2)
18.8 Documentation
623(4)
19 The "Sentinel": A Conceptual Nanomedical Strategy for the Enhancement of the Human Immune System 627(16)
Frank J. Boehm
Angelika Domschke
19.1 Introduction
627(1)
19.2 Brief Survey of Current Nanomedical Research: Toward Immune System Augmentation
628(3)
19.3 Conceptual "Sentinel" Nanomedical Platform for the Significant Enhancement of the Human Immune System
631(7)
19.4 Conclusion
638(5)
20 Immunotherapy for Gliomas and Other Intracranial Malignancies 643(14)
Mario Ganau
Gianfranco K.I. Ligarotti
Salvatore Chibbaro
Andrea Soddu
20.1 Regional Immunotherapy: A Rising Trend in Nanomedicine
643(2)
20.2 Primary and Secondary Brain Tumors
645(1)
20.3 Current Approaches to Immunotherapy for Brain Tumors
646(2)
20.4 Review of Ongoing Clinical Trials
648(1)
20.5 Neuro-Oncology and Immunotherapy: An Outlook for the Next 10 Years
649(8)
21 Engineering Nanoparticles to Overcome Barriers to Immunotherapy 657(42)
Randall Toy
Krishnendu Roy
21.1 Introduction
657(7)
21.2 Engineering Nanoparticles to Manipulate Transport and the Immune Response
664(6)
21.3 Improving Nanoparticle Design to Enhance Immunotherapy Efficacy
670(15)
21.4 Conclusions
685(14)
22 Metal-Based Nanoparticles and thelmmune System: Activation, Inflammation, and Potential Applications 699(32)
Yueh-Hsia Luo
Louis W. Chang
Pinpin Lin
22.1 Introduction
699(8)
22.2 Nanoparticles and Immune System
707(12)
22.3 Conclusion and Future Perspectives
719(12)
23 Silica Nanoparticles Effects on Hemostasis 731(22)
Volodymyr Gryshchuk
Volodymyr Chernyshenko
Tamara Chernyshenko
Olha Hornytska
Natalya Galagan
Tetyana Platonova
23.1 Introduction
731(1)
23.2 Materials and Methods
732(3)
23.3 Results
735(10)
23.4 Discussion
745(1)
23.5 Conclusions
746(7)
24 Valproate-Induced Rodent Model of Autism Spectrum Disorder: Immunogenic Effects and Role of Microglia 753(18)
Prabha S. Awale
James C.K. Lai
Srinath Pashikanthi
Alok Bhushan
24.1 Introduction
753(1)
24.2 Autism Spectrum Disorders: Etiology and Pathogenesis
754(1)
24.3 Valproate-Induced Rodent Model of Autism Spectrum Disorders
755(8)
24.4 Mechanism of Action of VPA
763(1)
24.5 Conclusions and Future Prospects
764(7)
25 Accelerated Blood Clearance Phenomenon and Complement Activation-Related Pseudoallergy: Two Sides of the Same Coin 771(30)
Amr S. Abu Lila
Janos Szebeni
Tatsuhiro lshida
25.1 Introduction
771(1)
25.2 Immunogenicity of Liposomal Drug Delivery Systems
772(5)
25.3 Features Distinguishing CARPA from Classical IgE-Mediated Immunity
777(1)
25.4 Mechanism of CARPA
777(4)
25.5 Factors Affecting Complement Activation by Liposomes
781(3)
25.6 Predictive Tests for CARPA
784(3)
25.7 Strategies to Attenuate/Abrogate CARPA
787(2)
25.8 Conclusions
789(12)
26 Current and Rising Concepts in Immunotherapy: Biopharmaceuticals versus Nanomedicines 801(34)
Matthias Bartneck
26.1 Immunity in Inflammatory Disease and Cancer
801(3)
26.2 Nanomedicine
804(4)
26.3 Therapeutic Modulation of Immunity
808(16)
26.4 Conclusions
824(11)
27 Characterization of the Interaction between Nanomedicines and Biological Components: In vitro Evaluation 835(32)
Cristina Fornaguera
27.1 Introduction
835(7)
27.2 Experimental Techniques for the Analysis of Nanoparticle Interaction with Biological Components
842(18)
27.3 Conclusions and Future Prospects
860(7)
28 Unwanted Immunogenicity: From Risk Assessment to Risk Management 867(26)
Cheryl Scott
28.1 Introduction
867(3)
28.2 Cause and Effect
870(2)
28.3 Evaluating Immunogenicity
872(6)
28.4 Predict and Prevent
878(8)
28.5 From Start to Finish-and Beyond
886(7)
29 Emerging Therapeutic Potential of Nanoparticles in Pancreatic Cancer: A Systematic Review of Clinical Trials 893(36)
Minnie Au
Theophilus I. Emeto
Jacinta Power
Venkat N. Vangaveti
Hock C. Lai
29.1 Introduction
894(2)
29.2 Methods Section
896(2)
29.3 Results
898(9)
29.4 Synthesis of Study Results
907(6)
29.5 Discussion
913(6)
29.6 Conclusions
919(10)
30 SGT-53: A Novel Nanomedicine Capable of Augmenting Cancer Immunotherapy 929(42)
Joe B. Harford
Sang-Soo Kim
Kathleen F. Pirollo
Antonina Rait
Esther H. Chang
30.1 Introduction
929(3)
30.2 The Role of p53 in Cancer
932(5)
30.3 Cancer Therapeutics Based on p53
937(1)
30.4 The Role of p53 as Guardian of Immune Integrity
938(1)
30.5 SGT-53, A Novel Nanomedicine for TP53 Gene Therapy
939(9)
30.6 SGT-53 Augments Cancer Immunotherapy Based on an Anti-PD1 Monoclonal Antibody
948(6)
30.7 Summary and Perspectives
954(17)
Index 971
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.