Applications And Engineering Of Monoclonal Antibodies

Front Cover
CRC Press, Nov 27, 1998 - Medical - 249 pages
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A valuable resource for researchers and workers in the fields of both pharmaceuticals and biotechnology as well as undergraduates in biochemistry, applied biology, biomedical sciences and pharmacy, this book compares established techniques of antibody production with the new. Antibody structure and the implications of antibody engineering are fully discussed, and a case study approach illustrates how antibodies are finding increasing use in the diagnosis and treatment of disease. The volume ends with commercial expression, purification and large-scale manufacture of antibodies and their future potential, particularly as therapeutic agents.
 

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Contents

Preparation Structure and Function of Monoclonal Antibodies 11 Introduction
1
12 The role of antibodies in the immune response
2
14 The organisation of antibody genes
11
15 Antigenbinding affinity and avidity 151 Affinity
13
152 Avidity
14
762 Human monoclonal antibodies
18
163 Human MAbs from transgenic mice
20
764 Isolation of antibodies by phage display
21
392 Radioimmunoguided surgery
116
Monoclonal Antibodies in Therapeutic Applications 41 Introduction
119
42 Cancer
120
421 Cancer therapy with unmodifed naked antibodies
121
422 Antiidiotype antibodies
123
423 Bispecific antibodymediated effector cell targeting
125
424 Other approaches to recruit the immune system using MAbs
127
425 Radioimmunotherapy
128

Antibody Engineering Design for Specific Applications 21 Introduction
27
22 Isolation of variable region genes
28
23 Overcoming immunogenicity
29
232 Antibody fragments to reduce immunogenicity
37
233 Chemical modification to reduce immunogenicity
38
234 Immunosuppressive therapy
40
242 Recombinant antibody fragments
42
Fabbased fragments
43
Fvbased fragments
45
Multivalent antibody fragments
48
25 Antibodies with multiple specificities
50
26 Engineering effector functions
54
Chemical conjugates
58
Sitespecific attachment
63
Fusion proteins
65
27 Engineering pharmacokinetics and biodistribution
67
277 Pharmacokinetics of IgG
68
272 Pharmacokinetics of antibody fragments
71
273 Clearance
74
274 Chemical modification
75
Monoclonal Antibodies in Research and Diagnostic Applications 31 Introduction
77
321 Radioimmunoassay
78
322 Immunoradiometric assay
79
323 Nonisotopic immunoassays
83
324 Improving sensitivity
85
325 Assay formats
89
326 Advantages of monoclonal antibodies in immunoassay
91
33 Immunosensors
92
33r Massdetecting immunosensors
93
332 Electrochemical immunosensors
94
333 Optical immunosensors
95
34 Immunocytochemistry
97
35 Flow cytometry and cell sorting FACS
99
36 Western blotting immunoblotting
100
37 Immunopurification
102
38 Antibodies in structural biology
106
391 Radioimmunodetection of human tumours
107
Form of antibody
109
Radioisotopes
110
Two and threestep targeting approaches
114
Form of antibody
129
Radioisotopes
132
Clearance mechanisms and twostep targeting
136
Clinical results with RIT
137
426 Immunotoxins
139
427 Drug conjugates
142
428 Antibodydirected enzyme prodrug therapy ADEPT
144
429 Vascular targeting
146
43 Infectious disease 431 Antiviral antibodies
147
432 Bacterial sepsis
148
447 Inhibition of platelet aggregation
149
442 Thrombolysis
150
45 Disorders of the immune systeminflammatory diseases 451 The inflammatory response
151
AntiTNF antibodies in rheumatoid arthritis and inflammatory bowel disease
153
AntiC5
154
454 Antibodies which directly inhibit T cell activation and proliferation
155
455 Antibody treatment of allergy
158
Production of Monoclonal Antibodies 51 Introduction
161
527 Transient expression systems
162
522 Stable expression systems
163
523 Expression of antibody fragments in mammalian cells
167
531 Intracellular expression of antibody fragments in E coli
168
532 Secretion of antibody fragments from E coli
170
54 Expression in other microbial systems
172
55 Expression in plants
173
56 Production in transgenic animals
174
57 Expression in insect cells
175
59 Purification of monoclonal antibodies 597 Purification of IgC
176
592 Purification of IgM
181
594 Purification for therapeutic use
185
Prospects for Engineered Antibodies in Biotechnology 61 Gene therapy 677 Intracellular antibodies
187
612 Other applications of MAbs in gene therapy
188
62 Applications of antibodies in plants
189
64 Towards drug design
190
65 Improving affinity
191
66 Summary and prospects
192
References
195
Index
241
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