Multivalent antibodies: when design surpasses evolution.
Evolutionary pressure has selected antibodies as key immune molecules acting against foreign pathogens. The development of monoclonal antibody technology has allowed their widespread use in research, real-time diagnosis and treatment of multiple diseases, including cancer. However, compared with hematologic malignancies, solid tumors have often proven to be relatively resistant to antibody-based therapies. In an attempt to improve the tumor-targeting efficacy of antibodies, new formats with modified, multivalent properties have been generated. Initially, these formats imitated the structure of native IgG, creating mostly monospecific, bivalent antibodies. Recently, novel trivalent antibodies have been developed to maximize tumor targeting capabilities through enhanced biodistribution and functional affinity. We review recent advances in the engineering of multivalent antibodies and further discuss their promise as agents for in vivo diagnostics and therapy.
Cuesta
Angel M
AM
Hospital Universitario Puerta de Hierro, 28222 Majadahonda, Madrid, Spain.
Sainz-Pastor
Noelia
N
Bonet
Jaume
J
Oliva
Baldomero
B
Alvarez-Vallina
Luis
L
D000906:Antibodies; D019020:Directed Molecular Evolution; D016503:Drug Delivery Systems; D009369:Neoplasms / Q000188:drug therapy; D015202:Protein Engineering; D055503:Protein Multimerization; D011994:Recombinant Proteins
D000906:Antibodies; D011994:Recombinant Proteins