Targeting CD20 in follicular NHL: novel anti-CD20 therapies, antibody engineering, and the use of radioimmunoconjugates.
Rituximab (chimeric anti-CD20 monoclonal antibody) is widely employed in the treatment of patients with B cell non-Hodgkin lymphoma (NHL). This agent has activity in both indolent and aggressive disease, alone and in combination with chemotherapy. Unfortunately, however, many patients develop resistant disease. Ongoing efforts to improve outcomes include changes in dose and schedule, as well as the use of other biologic agents or antibodies that may enhance activity when administered together with rituximab. A relatively new focus is the development of engineered anti-CD20 antibodies that are optimized for their capability to mediate antibody-mediated cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). Human or humanized structures have also been employed to potentially improve these attributes, as well as to improve on pharmacokinetics and immunogenicity. Other studies in NHL have clearly demonstrated that radiolabeled anti-CD20 antibodies (such as I-131 tositumomab and Y-90 ibritumomab tiuxetan) may be useful in relapsed and refractory disease, and have potential utility as part of initial treatment as well. Further studies of these modified anti-CD20 antibodies are ongoing in order to optimize their use for maximal clinical benefit.
Leonard
John P
JP
Center for Lymphoma and Myeloma, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY 0021-4805, USA. jpleonar@mail.med.cornell.edu
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003601:Cytotoxicity Tests, Immunologic; D019008:Drug Resistance, Neoplasm / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000276:immunology* / Q000532:radiotherapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000276:immunology; D016499:Radioimmunotherapy / Q000379:methods; D000069283:Rituximab; D015021:Yttrium Radioisotopes / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D007155:Immunologic Factors; D007457:Iodine Radioisotopes; D015021:Yttrium Radioisotopes; D000069283:Rituximab; C422802:ibritumomab tiuxetan; C119496:tositumomab I-131