Developing costimulatory molecules for immunotherapy of diseases / Manzoor Ahmad Mir.

Format:

Book

Author/Creator:

Mir, Manzoor Ahmad, author.

Language:

English

Subjects (All):

Immunologic diseases--Treatment.

Immunologic diseases.

Cellular therapy.

Immunotherapy.

Physical Description:

1 online resource : color illustrations

Place of Publication:

London : Academic Press is an imprint of Elsevier, [2015]

System Details:

Mode of access: World Wide Web.

text file

Summary:

Developing Costimulatory Molecules for Immunotherapy of Diseases highlights the novel concept of reverse costimulation, which can be effectively exploited to develop immunotherapy using either humanized antibodies against CD80, CD86, and other costimulatory molecules or CD28 fusinogenic proteins in the treatment of diseases, like allergies, asthma, rheumatoid arthritis, multiple sclerosis, lupus nephritis, severe psoriasis, vulgaris tuberculosis, typhoid, transplantation, cancer, and inflammation. Considering the importance of complex roles played by CD28 and B7 costimulatory families in regulating the immune systems, novel approaches targeting these families will yield new therapies for the treatment of numerous diseases. To translate this field into the clinic, there is an urgent need to develop novel methods to target the currently-appreciated costimulatory pathway and deeply understand the pathophysiology of the diseases involving costimulatory molecules. Despite the complex roles and interactions within the CD28 and B7 costimulatory families, the novel approaches targeting these families will yield new therapies for the treatment of inflammation, autoimmunity, transplantation, cancer, and other infectious diseases. Describes the breakthrough strategy of immunotherapy involving costimulatory molecules to treat various diseases, minimizing side effects inflicted by drug therapies, Contains many flowcharts and diagrams highlighting costimulatory interactions, Provides cutting edge knowledge on costimulation and immunotherapy with relation to different diseases and their treatment, Includes coverage of therapeutic and preventative methods, Brings the basic science and clinical perspectives together in a single volume, facilitation translational possibilities, Helps to integrate the value of costimulation immunotherapy outside of a cancer setting Book jacket.

Contents:

1 Introduction to Costimulation and Costimulatory Molecules 1

Introduction 1

Costimuiatory Molecules 3

Two-Signal Model of T-Cell Activation 5

The B7 Family of Costimulatory Ligands 7

CD80 Costimuiatory Molecule 12

CD86 Costimulatory Molecule 12

CD80 and CD86 Expression Kinetics 13

CD80 and CD86 Binding Kinetics to CD28 and CTLA-4 14

Different Oligomeric States of CD80 and CD86 14

PD-L1/B7-H1 Costimulatory Molecule 15

B7-H2/B7RP-1/LICOS Costimulatory Molecule 17

B7-DC/PD-L2 Costimulatory Molecule 17

B7-H3 Costimuiatory Molecule 18

B7-H4 or B7×/B7S1 Costimulatory Molecule 19

CD28 Molecule 20

CTLA-4 Molecule 20

ICOS Molecule 21

The Programmed Death-1 23

CD40 Costimulatory Molecule 24

CD40L/CD154 Costimulatory Molecule 25

Pathways in the TIMFR/TNF Family 25

4-1BB/4-1BBL 28

OX40/OX40L 29

HVEMLIGHT 30

ICOS, GITR, and CD27/CD70 31

Summary 31

References 33

2 Concept of Reverse Costimulation and Its Role in Diseases 45

Introduction 45

Concept of Bidirectional Costimulation 46

Reverse Costimulation of APCs 50

Role of CD80 and CD86 in the Costimulation of B Cells 51

Role of Bidirectional Costimulation in the Activation of DCs 54

Role of Reverse Costimulation on Macrophages 58

Application of Reverse Costimulation in Diseases 60

Reverse Costimulation Through CD80 (B7-1) 61

Reverse Costimulation Through CTLA-4 64

B7-DC Reverse Costimulation 65

Reverse Costimulation Through CD40L/CD40 66

Reverse Signaling Through CD137L/CD137 68

Role of Reverse Costimulation in Cancer 69

References 74

3 Costimulation Immunotherapy in Infectious Diseases 83

Introduction 83

Costimulation Biology Modulation by Pathogens 89

Modulation of Costimulatory Molecules by Viruses 92

Modulation of Costimulatory Molecules by Bacteria 93

Modulation of Costimulatory Molecules by Protozoan Parasites 96

Costimulatory Molecules in Therapeutic Vaccination 96

Therapeutic Vaccination Using Costimulatory Molecules in HIV 98

B7 Costimulatory Molecules in Infectious Diseases 99

Costimulatory Molecules in Allergies and Asthma 101

Involvement of the B7:CD28 Family Molecules in the Regulation of Allergic Diseases 103

Regulation of the Immune Responses to Pathogens Through Costimulatory Molecules 107

Expression of Coinhibitory Molecules on Effector T Cells 108

Role of Coinhibitory Molecules in the Contraction of the Effector Phase of Immune Responses 109

Functional Exhaustion and Loss of Effector Functions 110

Potential Therapeutic Applications of Costimulatory Molecules in Infections 113

Summary 114

References 117

4 Costimulation Immunotherapy in Allergies and Asthma 131

Introduction 131

Immunology of Allergy and Asthma 132

Pathophysiology of Asthma 134

Response to Allergens in Asthma 134

Phenotypic Variability in Asthma 137

Role of Mast Cells in Allergy and Asthma 138

Immunotherapy to Allergens 139

Subcutaneous IT 140

Sublingual IT 141

Experimental IT Approaches 142

Peptide-Based Therapies 143

Allergen-Specific Therapy with Th1-Stimulating Adjuvants 144

Novel Approaches to Allergen-SIT 145

Current Immunomodulatory Strategies for Asthma Under Investigation 146

Monoclonal Anti-IgE Antibody Therapy 147

IgE-Binding Receptors 149

Anti-IgE Monoclonal Antibodies 149

sIL-4R Therapy 150

Targeting Tregs for IT of Allergy and Asthma 151

Costimulation in Allergy and Asthma 153

Costimulation in Asthma 154

Costimulation and T-Cell Reactivity to Allergens 156

What Makes Costimulatory Molecules a Promising Target in Allergy and Asthma? 160

T-Cell Specificity 160

Expression on T Cells 162

Predominant Involvement in Secondary Immune Reactions 162

Positive Regulatory Signal 163

Th2 T-Cell Bias 163

Targeting Costimulatory Molecules for Treatment of Allergen-Induced Airway Inflammation 163

Targeting B7-CD28 Costimulatory Pathway 164

Targeting PD-1, PD-L1/PD-L2 Costimulatory Pathway 167

Targeting ICOS 1 169

Targeting OX40 169

Targeting BTLA-4 169

Tools for Modulation of Costimulatory Signals 170

Administration of Immune Modulators 170

Blockade Versus Elimination of Allergen-Specific T Cells 171

References 172

5 Costimulation in Lymphomas and Cancers 185

Introduction 185

Major Costimulatory and Coinhibitory Pathways in Antitumor Immunity 186

Targeting T Cell Costimulatory Molecules to Improve Antitumor Immunity 188

B7 Superfamily of Costimulatory Molecules in Antitumor Immunotherapy 194

B7-1/B7-2:CD28/CTLA-4 194

Fully Humanized Anti-CTLA-4 Antibody in Treatment of Tumors 210

Ipilimumab (Fully Humanized Anti-CTLA-4 Antibody) in the Treatment of Tumors 210

Tremelimumab (Fully Humanized Anti-CTLA-4 Antibody) in the Treatment of Tumors 212

CD279 (PD-1), CD274 (PD-L1), and CD273 (PD-L2) Expression in Malignancy 213

Therapeutic Modulation of PD-1 (CD274), PDL-1 (CD279), and PDL-2 (CD273) 214

TNF:TNFR Superfamily of Costimulatory Molecules in Antitumor Immunity 220

CD40L:CD40 Costimulatory Pathway 220

1BBL:4-1BB Costimulatory Pathway 222

OX40:OX40L Costimulatory Pathway 223

Light: HVEM Costimulatory Pathway 224

CD70:CD27 Costimulatory Pathway 225

GITRL:CITR Costimulatory Pathway 226

CD30L:CD30 Costimulatory Pathway 226

Costimulation Immunotherapy and Tumor Tolerance 227

Modulation of B7 Pathway to Augment Cancer Immunotherapy 229

Allogenic HSCT 230

Tumor Vaccination Strategies 230

Bioengineering of T Cells for Cancer Immunotherapy 231

1COS and B7-H2 Costimulatory Pathway in Cancer 231

Therapeutic Modulation of ICOS/ICOS-L 232

Combination of Costimulatory Antibody-Ligand Fusion Proteins for Targeted Cancer Immunotherapy 232

Summary and Conclusion 234

References 237

6 T-Cell Costimulation and Its Applications in Diseases 255

Introduction to T-Cell Costimulation 255

Costimulation Mediated by CD28 Costimulatory Pathway in T Cells 256

CD28 Costimulation Enhances T-Cell Survival 256

CD28 T-Cell Costimulation in Diseases 257

CD28 Costimulation in Primary T-Cell Responses 257

CD28-B7 Costimulation and Its Effect on CD8+ Memory T-Cell Responses 259

The Future Prospectus 260

Concluding Remarks 262

Unanswered Questions 264

Promoting T-Cell Function by Modulating Costimulation or Co-inhibition 264

Turning on the Stimulators: Antibodies to 4-1BB (CD137), OX40 (134), GITR, and CD40 265

Turning Off the Brakes: Antibodies Against CTLA-4 (CD152), PD-1 (CD279), and PD-L1 266

Adoptive T-Cell Transfer 268

Improving Signaling Capacities-Second- and Third-Generation CARs 269

First-Generation CARs 272

Second-Generation CARs 273

Third-Generation CARs 274

CAR T Cells in Clinical Trials 280

References 281.

Notes:

Online resource; title from PDF title page (Ebsco, viewed June 3, 2015).

Includes bibliographical references and index.

ISBN:

9780128026755

0128026758

OCLC:

910324332

Access Restriction:

Restricted for use by site license.