[Therapeutic monoclonal antibodies in onco-hematology].
Rituximab, a chimeric monoclonal anti-CD20 antibody, was introduced into clinical practice in 1997, and has proven to be highly effective in the treatment of B-lymphoproliferative disorders and autoimmune diseases. Despite such success, in vivo mechanisms of action of anti-CD20 have only recently began to be unraveled, pointing to the crucial role of antibody-dependent cellular cytotoxicity response mediated through Fcg receptor signalling. Better understanding of pharmacokinetics and factors influencing individual exposure mediated through anti-CD20 will allow to engineer these molecules to increase their effector responses. Meanwhile, other formats have also been investigated, such as radiolabeled anti-CD20, or coupling of antibodies to cytotoxic drugs such as anti-CD33 used in myeloid leukemia. However these antibodies are used in combination with standard chemotherapy and cannot substitute for cytotoxic drugs. This review summarizes the knowledge acquired through our clinical use of anti-CD20 and authorized monoclonal antibodies in oncohematology and proposes some news areas that will lead to the development of new and more effective therapeutic strategies.
Cartron
Guillaume
G
Service d'hématologie et biothérapies, Centre d'investigation clinique biothérapies, CHU de Montpellier, 191, avenue du doyen Gaston Giraud, 34295 Montpellier, France. g-cartron@chu-montpellier.fr
Rossi
Jean-François
JF
D000074323:Alemtuzumab; D000617:Aminoglycosides / Q000276:immunology / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology; D018951:Antigens, CD20 / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000074301:CD52 Antigen; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D000079982:Gemtuzumab; D006023:Glycoproteins / Q000276:immunology; D006402:Hematologic Diseases / Q000188:drug therapy* / Q000276:immunology / Q000532:radiotherapy; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D000922:Immunotoxins / Q000008:administration & dosage / Q000627:therapeutic use; D008232:Lymphoproliferative Disorders / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000532:radiotherapy; D000069283:Rituximab; D063268:Sialic Acid Binding Ig-like Lectin 3
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D018951:Antigens, CD20; D015214:Antigens, Differentiation, Myelomonocytic; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C571163:CD33 protein, human; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D018796:Immunoconjugates; D000922:Immunotoxins; D063268:Sialic Acid Binding Ig-like Lectin 3; D000074323:Alemtuzumab; D000069283:Rituximab; C422802:ibritumomab tiuxetan; D000079982:Gemtuzumab