List of Corresponding Authors |
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xxvii | |
Foreword |
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xxix | |
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My Life with Biologicals and Nanodrugs: A Twenty-Year Affair |
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xxxvii | |
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1 Current Immune Aspects of Biologics and Nanodrugs: An Overview |
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1 | (82) |
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3 | (18) |
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1.2 Biologics versus Small-Molecule Drugs |
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21 | (3) |
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24 | (8) |
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1.4 Are Biologics and Nanodrugs Adversely Immunogenic? |
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32 | (19) |
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1.5 Immunogenicity Assessment of Biologics and Nanodrugs |
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51 | (5) |
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1.6 Entering the Era of Biosimilars |
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56 | (6) |
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1.7 Immune Aspects of Biosimilars and Nanosimilars: The Copaxone® Example |
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62 | (5) |
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1.8 Concluding Remarks and Future Directions |
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67 | (16) |
2 Immunological Issues with Medicines of Nano Size: The Price of Dimension Paradox |
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83 | (40) |
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2.1 Adverse Immune Effects of Nanodrugs |
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84 | (10) |
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2.2 Issues of Terminology |
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94 | (2) |
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2.3 Adverse Immune Effects of Nanodrugs: The Dimension Paradox |
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96 | (15) |
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2.4 Vicious Cycle between Specific and Nonspecific Immune Responses to Nanodrugs |
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111 | (1) |
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2.5 CARPA as Blood Stress |
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112 | (2) |
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114 | (9) |
3 Immunotherapy and Vaccines |
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123 | (32) |
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123 | (1) |
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124 | (4) |
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3.3 Nanotechnology in Vaccines |
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128 | (17) |
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145 | (10) |
4 Site-Specific Antibody Conjugation for ADC and Beyond |
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155 | (28) |
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155 | (4) |
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4.2 Site-Specific ADC through Specific Amino Acids |
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159 | (2) |
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4.3 Site-Specific ADC through Unnatural Amino Acids |
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161 | (3) |
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4.4 Site-Specific ADC through Glycans |
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164 | (1) |
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4.5 Site-Specific ADC through Short Peptide Tags |
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165 | (1) |
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4.6 Site-Specific Antibody Conjugation for Diagnosis |
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166 | (3) |
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4.7 Site-Specific Antibody Conjugation for Other Therapeutic Applications |
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169 | (4) |
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173 | (10) |
5 Current Understanding of Interactions between Nanoparticles and the Immune System |
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183 | (46) |
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184 | (4) |
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188 | (11) |
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199 | (5) |
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204 | (4) |
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208 | (21) |
6 Auto-antibodies as Biomarkers for Disease Diagnosis |
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229 | (20) |
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229 | (1) |
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6.2 Auto-antibodies as Biomarkers |
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230 | (3) |
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6.3 Auto-antibodies for Companion Diagnostics Enabling Personalized Medicine |
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233 | (2) |
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6.4 Biomarker Discovery Strategies |
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235 | (4) |
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6.5 Antigen/Auto-antibody Interactions as Biomarker Candidates |
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239 | (3) |
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6.6 Diagnostic Assays Based on Antigen/Auto-antibody Interactions |
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242 | (1) |
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243 | (6) |
7 The Acceleated Blood Clearance Phenomenon of PEGylated Nanocarriers |
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249 | (40) |
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249 | (2) |
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7.2 Mechanism of ABC Phenomenon |
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251 | (3) |
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7.3 Correlation Between Complement Activation and ABC Phenomenon |
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254 | (2) |
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7.4 Factors That Affect the Magnitude of the ABC Phenomenon |
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256 | (14) |
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7.5 Strategies to Abrogate/Attenuate Induction of the ABC Phenomenon |
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270 | (5) |
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7.6 Clinical Implications of ABC Phenomenon |
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275 | (1) |
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276 | (13) |
8 Anti-PEG Immunity Against PEGylated Therapeutics |
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289 | (22) |
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289 | (1) |
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8.2 PEG Immunogenicity in Animal Models |
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290 | (3) |
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8.3 PEG lmmunogenicity in Humans |
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293 | (5) |
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8.4 Properties of Anti-PEG Antibody Epitope |
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298 | (1) |
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8.5 Strategies to Avert Anti-PEG Antibody Responses |
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299 | (2) |
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301 | (10) |
9 Complement Activation: Challenges to Nanomedicine Development |
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311 | (30) |
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311 | (1) |
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9.2 C Activation Pathways and Downstream Effectors |
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312 | (2) |
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9.3 Role of C in Human Health and Disease |
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314 | (2) |
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9.4 Complement Activation by Biomaterials |
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316 | (1) |
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9.5 Nanomedicine-Mediated C Activation |
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317 | (2) |
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9.6 Current Methods to Measure Nanomedicine-Mediated C Activation |
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319 | (9) |
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328 | (13) |
10 Intravenous Immunoglobulin at the Borderline of Nanomedicines and Biologicals: Antithrombogenic Effect via Complement Attenuation |
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341 | (20) |
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341 | (2) |
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343 | (4) |
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10.3 Antiphospholipid Syndrome |
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347 | (4) |
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351 | (2) |
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10.5 Mechanism of IVIG Modulation of Vaso-Occlusive Disorders |
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353 | (2) |
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355 | (6) |
11 Lessons Learned from the Porcine CARPA Model: Constant and Variable Responses to Different Nanomedicines and Administration Protocols |
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361 | (28) |
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11.1 Introduction: CARPA as an Immune-Mediated Stress Reaction in Blood Triggered by Nanomedicines |
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361 | (2) |
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11.2 In vitro Tests for CARPA |
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363 | (1) |
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11.3 Animal Models of Immune Toxicity: Which Is Good for CARPA Evaluation? |
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363 | (1) |
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11.4 Non-Standard Immunotoxicity Tests of CARPA in Different Animals |
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364 | (2) |
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11.5 The Use of Pigs as Disease Models |
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366 | (1) |
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11.6 Technical Details of the Porcine CARPA Model |
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366 | (1) |
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367 | (2) |
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11.8 Uniqueness of the Porcine CARPA Model |
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369 | (1) |
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11.9 Invariable Parameters of Porcine CARPA |
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369 | (2) |
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11.10 Variable Parameters of Porcine CARPA |
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371 | (5) |
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11.11 Summary and Future Directions |
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376 | (13) |
12 Blood Cell Changes in Complement Activation-Related Pseudoallergy: Intertwining of Cellular and Humoral Interactions |
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389 | (28) |
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389 | (1) |
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12.2 Blood Cell Changes in CARPA: Human and Animal Data |
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390 | (3) |
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12.3 Platelets and Their Role in CARPA |
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393 | (6) |
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12.4 Zooming on Interactions, Receptors and Mediators in CARPA-Associated Blood Cell Changes |
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399 | (8) |
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407 | (10) |
13 Rodent Models of Complement Activation-Related Pseudoallergy: Inducers, Symptoms, Inhibitors and Reaction Mechanisms |
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417 | (24) |
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417 | (1) |
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13.2 The CARPA genic Effects of CVF, Zymosan and LPS in Rodents and Their Modulation with Complement Antagonists |
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418 | (2) |
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420 | (1) |
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13.4 Characteristics of Liposome-Induced CARPA in Rats |
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420 | (6) |
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13.5 Effects of Complement Components C3a and C5a in the Guinea Pig |
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426 | (2) |
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13.6 Effects of Complement Components C3a and C5a in the Rat |
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428 | (1) |
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13.7 Effects of Complement Components C3a and C5a in the Rabbit, Hamster and Mouse |
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429 | (2) |
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431 | (10) |
14 Immune Reactions in the Delivery of RNA Interference-Based Therapeutics: Mechanisms and Opportunities |
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441 | (32) |
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441 | (4) |
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14.2 Overview of Approaches for Efficient Intracellular Delivery of siRNA |
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445 | (7) |
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14.3 Immune Reactions Elicited during RNAi Therapy |
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452 | (4) |
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14.4 Recent Advancements in Predicting Immunological Complications |
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456 | (6) |
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14.5 Conclusions and Future Perspectives |
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462 | (11) |
15 Lipid Nanoparticle Induced Immunomodulatory Effects of siRNA |
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473 | (34) |
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473 | (1) |
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474 | (3) |
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15.3 Strategies for Delivering siRNA |
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477 | (2) |
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15.4 Immune Response to siRNA Payload and Its Modulation |
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479 | (12) |
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491 | (3) |
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494 | (13) |
16 Nanovaccines against Intracellular Pathogens Using Coxiella burnetii as a Model Organism |
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507 | (30) |
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507 | (1) |
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16.2 Using Nanomedicine to Tackle Intracellular Pathogens |
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508 | (1) |
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16.3 C. burnetii Bacteriology |
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509 | (1) |
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16.4 Epidemiology and Clinical Manifestations |
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509 | (1) |
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510 | (2) |
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16.6 Immune Evasion Strategies |
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512 | (2) |
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16.7 Qvax® and Correlates of Protective Immunity |
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514 | (2) |
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516 | (6) |
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16.9 Why Are Nanoparticle Vaccines a Good Strategy for C. burnetii? |
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522 | (15) |
17 Immunogenicity Assessment for Therapeutic Protein Products |
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537 | (48) |
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538 | (1) |
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539 | (1) |
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17.3 Clinical Consequences |
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540 | (5) |
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17.4 Recommendations for Immunogenicity Risk Mitigation in the Clinical Phase of Development of Therapeutic Protein Products |
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545 | (4) |
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17.5 Patient-and Product-Specific Factors That Affect Immunogenicity |
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549 | (18) |
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567 | (18) |
18 Assay Development and Validation for Immunogenicity Testing of Therapeutic Protein Products |
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585 | (42) |
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586 | (1) |
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587 | (1) |
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588 | (3) |
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18.4 Assay Design Elements |
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591 | (17) |
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608 | (7) |
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615 | (6) |
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18.7 Implementation of Assay Testing |
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621 | (2) |
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623 | (4) |
19 The "Sentinel": A Conceptual Nanomedical Strategy for the Enhancement of the Human Immune System |
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627 | (16) |
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627 | (1) |
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19.2 Brief Survey of Current Nanomedical Research: Toward Immune System Augmentation |
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628 | (3) |
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19.3 Conceptual "Sentinel" Nanomedical Platform for the Significant Enhancement of the Human Immune System |
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631 | (7) |
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638 | (5) |
20 Immunotherapy for Gliomas and Other Intracranial Malignancies |
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643 | (14) |
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Gianfranco K.I. Ligarotti |
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20.1 Regional Immunotherapy: A Rising Trend in Nanomedicine |
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643 | (2) |
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20.2 Primary and Secondary Brain Tumors |
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645 | (1) |
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20.3 Current Approaches to Immunotherapy for Brain Tumors |
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646 | (2) |
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20.4 Review of Ongoing Clinical Trials |
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648 | (1) |
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20.5 Neuro-Oncology and Immunotherapy: An Outlook for the Next 10 Years |
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649 | (8) |
21 Engineering Nanoparticles to Overcome Barriers to Immunotherapy |
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657 | (42) |
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657 | (7) |
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21.2 Engineering Nanoparticles to Manipulate Transport and the Immune Response |
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664 | (6) |
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21.3 Improving Nanoparticle Design to Enhance Immunotherapy Efficacy |
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670 | (15) |
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685 | (14) |
22 Metal-Based Nanoparticles and thelmmune System: Activation, Inflammation, and Potential Applications |
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699 | (32) |
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699 | (8) |
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22.2 Nanoparticles and Immune System |
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707 | (12) |
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22.3 Conclusion and Future Perspectives |
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719 | (12) |
23 Silica Nanoparticles Effects on Hemostasis |
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731 | (22) |
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731 | (1) |
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23.2 Materials and Methods |
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732 | (3) |
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735 | (10) |
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745 | (1) |
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746 | (7) |
24 Valproate-Induced Rodent Model of Autism Spectrum Disorder: Immunogenic Effects and Role of Microglia |
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753 | (18) |
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753 | (1) |
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24.2 Autism Spectrum Disorders: Etiology and Pathogenesis |
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754 | (1) |
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24.3 Valproate-Induced Rodent Model of Autism Spectrum Disorders |
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755 | (8) |
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24.4 Mechanism of Action of VPA |
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763 | (1) |
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24.5 Conclusions and Future Prospects |
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764 | (7) |
25 Accelerated Blood Clearance Phenomenon and Complement Activation-Related Pseudoallergy: Two Sides of the Same Coin |
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771 | (30) |
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771 | (1) |
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25.2 Immunogenicity of Liposomal Drug Delivery Systems |
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772 | (5) |
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25.3 Features Distinguishing CARPA from Classical IgE-Mediated Immunity |
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777 | (1) |
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777 | (4) |
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25.5 Factors Affecting Complement Activation by Liposomes |
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781 | (3) |
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25.6 Predictive Tests for CARPA |
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784 | (3) |
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25.7 Strategies to Attenuate/Abrogate CARPA |
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787 | (2) |
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789 | (12) |
26 Current and Rising Concepts in Immunotherapy: Biopharmaceuticals versus Nanomedicines |
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801 | (34) |
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26.1 Immunity in Inflammatory Disease and Cancer |
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801 | (3) |
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804 | (4) |
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26.3 Therapeutic Modulation of Immunity |
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808 | (16) |
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824 | (11) |
27 Characterization of the Interaction between Nanomedicines and Biological Components: In vitro Evaluation |
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835 | (32) |
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835 | (7) |
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27.2 Experimental Techniques for the Analysis of Nanoparticle Interaction with Biological Components |
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842 | (18) |
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27.3 Conclusions and Future Prospects |
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860 | (7) |
28 Unwanted Immunogenicity: From Risk Assessment to Risk Management |
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867 | (26) |
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867 | (3) |
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870 | (2) |
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28.3 Evaluating Immunogenicity |
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872 | (6) |
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878 | (8) |
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28.5 From Start to Finish-and Beyond |
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886 | (7) |
29 Emerging Therapeutic Potential of Nanoparticles in Pancreatic Cancer: A Systematic Review of Clinical Trials |
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893 | (36) |
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894 | (2) |
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896 | (2) |
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898 | (9) |
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29.4 Synthesis of Study Results |
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907 | (6) |
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913 | (6) |
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919 | (10) |
30 SGT-53: A Novel Nanomedicine Capable of Augmenting Cancer Immunotherapy |
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929 | (42) |
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929 | (3) |
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30.2 The Role of p53 in Cancer |
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932 | (5) |
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30.3 Cancer Therapeutics Based on p53 |
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937 | (1) |
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30.4 The Role of p53 as Guardian of Immune Integrity |
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938 | (1) |
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30.5 SGT-53, A Novel Nanomedicine for TP53 Gene Therapy |
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939 | (9) |
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30.6 SGT-53 Augments Cancer Immunotherapy Based on an Anti-PD1 Monoclonal Antibody |
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948 | (6) |
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30.7 Summary and Perspectives |
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954 | (17) |
Index |
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971 | |