ABSTRACT
Reengineered and fully human monoclonal antibodies 1501 generated by recombinant DNA techniques – better suited for humans
Technologies mimicking somatic hypermutation – 1502 potential improvement in the antigen-binding affinity of monoclonal antibodies
Modifying the Fc portion of monoclonal antibodies – 1503 potential improvement in pharmacokinetics and therapeutic efficacy
Next generation of monoclonal antibodies 1503 Unconjugated monoclonal antibodies 1504 Anti-CD20 (rituximab) 1504 Second-generation anti-CD20 antibodies 1507 Alemtuzumab 1508 Anti-CD22 (epratuzumab) 1509 Anti-CD23 1509 Anti-CD80 1509 Anti-CD74 1509
Anti-HLA-DR 1511 Anti-CD30 1511 Anti-CD40 1511 Anti-CD19 1511 Anti-CD2 1511 Anti-CD4 1511 Anti-vascular endothelial growth factor 1512 Anti-CD47 1512 Bispecific antibodies 1512 Conjugated monoclonal antibodies 1513 Radioimmunotherapeutics 1513 Pretargeting radioimmunotherapy 1514 Drug immunoconjugates 1514 Immunotoxins 1515 Immunoliposomes 1515 Conclusions 1516 Key points 1516 References 1516
Excellent target specificity and a favorable safety profile have been major underpinnings behind over three decades of intensive effort to add immunotherapy and radioimmunotherapy (RIT), novel treatments, to the cancer armamentarium. Since the introduction of the first therapeutic mouse-derived antibody in 1986, there have been major advances in the understanding of mechanism of action and safety profile of monoclonal antibodies (mAbs). In the first advancement, ‘chimerization’ and ‘humanization’ have improved safety profiles and efficacy. Development of commercial production made the antibody a serious contender in the therapeutic arena. Monoclonal antibodies, either in their native form or conjugated to therapeutic agents, have wide utilities in managing lymphoid malignancies largely because these agents have favorable pharmacokinetics (PK) in humans, are often very specific to certain cell types, and
with a broad range of chemotherapeutics to suit various clinical settings.
