Contents

Introduction 66

Antibody Technology 66

Antibodies That Are Approved and in Late-Stage Clinical

Development 66

Promising Antibodies and Targets 67

Supportive Care 70

Novel Antibody Target Discovery in the Genomics and Proteomics Age 71

Approaches to Enhancing Antibody Efficacy 72

Enhancing Antibody Immune-Effector Functions 72

General Description of FcyRs 73

Preclinical and Clinical Evidence for the Importance of Fc yRs in

Antibody Therapy 74

Choosing an IgG Isotype 74

Amino Acid Sequence Variants 75

Fc Glycan Optimization 76

The Fc yR-Dependent Avidity Effect 77

Enhanced Complement Activity 77

Immunoconjugates as Cancer Therapeutics 78

Targeting Molecule 78

Cytotoxins 78

Linker 79

Acid-Labile Linkages 79

Sulfhydryl Linkages 80

Enzyme-Degradable Linkages 81

Enhancing Drug Delivery through Ligand-Targeted Liposomes 81

Conclusions 84

References 84

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