[Bispecific antibodies: what future?].
Monoclonal antibodies have emerged as a very successful class of therapeutic agents. In their native format, monoclonal antibodies are monospecific in that they recognize only one epitope, but their Fc domain also binds to FcfR-expressing cells. Attempts to improve the cytotoxicity of antibodies, particularly in the cancer field, have led to the design of bispecific antibodies: this can occur through various strategies, such as quadroma, thioether-linked Fab' gamma fragments or genetic engineering. Such bispecific antibodies have been developped to enhance immunotherapy, by bridging tumor cells and T cells, or radioimmunotherapy by combining bispecific antibodies and radiolabeled bivalent haptens that bind cooperatively to target cells. Multiple further applications can be envisaged such as targeting two different antigens on the same cell, or two epitopes of the same antigen. Although progresses have been slowed by technical constraints, there is little doubt that this class of novel antibodies derivatives will experience a promising development.
Pèlegrin
André
A
Institut de recherche en cancérologie de Montpellier (IRCM), Montpellier, F-34298, France ; Inserm U896, Montpellier, F-34298, France. andre.pelegrin@inserm.fr
Robert
Bruno
B
D018033:Antibodies, Bispecific / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity; D000970:Antineoplastic Agents / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D001360:Avidin; D001710:Biotin; D016503:Drug Delivery Systems; D015195:Drug Design; D000939:Epitopes / Q000276:immunology; D005544:Forecasting; D006241:Haptens / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology; D009369:Neoplasms / Q000276:immunology; D015202:Protein Engineering; D013329:Structure-Activity Relationship
D018033:Antibodies, Bispecific; D000970:Antineoplastic Agents; D000939:Epitopes; D006241:Haptens; D007128:Immunoglobulin Fragments; D009363:Neoplasm Proteins; D001360:Avidin; D001710:Biotin