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Cardiovascular & Hematological Agents in Medicinal Chemistry

Eiditor-in-Chief

ISSN (Print): 1871-5257
ISSN (Online): 1875-6182

Treatment of Acute Leukaemias with Monoclonal Antibodies: Current Status and Future Prospects

Author(s): G. Leone, S. Sica, M. T. Voso, S. Rutella and L. Pagano

Volume 4 , Issue 1 , 2006

Page: [33 - 52] Pages: 20

DOI: 10.2174/187152506775268820

Price: $58

Abstract

Monoclonal antibodies are a new class of agents targeted at specific receptors on cancer cells. In addition to direct cellular effects, antibodies can carry substances to the targeted cells, such as radioactive isotopes, toxins, and antineoplastic agents. At present monoclonal antibodies, directed against both lymphoid antigens (CD 20 and CD 52) and a myeloid antigen (CD33) are available for clinical use. In ALL, rituximab, a humanised anti CD20 antibody, has been combined to chemotherapy mainly in mature B-ALL and Burkitts lymphoma and preliminary results are promising. Alemtuzumab is an anti-CD52 humanised antibody, which showed anti-tumour activity in CLL; clinical effects were observed in some patients with relapsed adult ALL. Monoclonal antibodies against myeloid antigens have been prevalently used in acute myeloid leukaemias (AML), where the most utilised immunological target is CD33. The CD33 molecule is expressed by approximately 90% of AMLs but not on CD34+ bone marrow-resident hematopoietic stem cells. The humanised anti-CD33 monoclonal antibody HuM195 has only modest activity against overt AML, but it can eliminate minimal residual disease. Radioimmunotherapy with β-particle-emitting isotopes targeting CD33 shows a major efficacy. Targeted chemotherapy with the anti-CD33-calicheamicin construct gemtuzumab ozogamicin (GO) has produced remissions as a single agent in patients with relapsed AML and appears promising when used in combination with standard chemotherapy. GO is composed of a humanised immunoglobulin G4 (IgG4) monoclonal antibody (mAb), targeting the CD33 antigen and linked to a calicheamicin derivative, a cytotoxic anthracycline antibiotic. GO has been approved by FDA as second-line therapy in older patients with AML. The most common adverse effects of monoclonal antibodies are myelosuppression, infusion-related reactions, and hypersensitivity reactions. Rituximab may cause tumour lysis syndrome. Alemtuzumab causes immunosuppression, increasing the risk of infection. GO may cause hepatotoxicity.

Keywords: AML, ALL, monoclonal antibodies, myeloid antigens, lymphoid antigens, gemtuzumab ozogamicin, alemtuzumab, rituximab


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