Antibody-based therapy of leukaemia

John C. Morris; Thomas A. Waldmann

doi:10.1017/S1462399409001215

Antibody-based therapy of leukaemia

Published online by Cambridge University Press: 01 September 2009

John C. Morris and

Thomas A. Waldmann

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John C. Morris*: Affiliation:
Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MDUSA.
Thomas A. Waldmann: Affiliation:
Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MDUSA.
*: *Corresponding author: John C. Morris, Co-Director Clinical Trials, Metabolism Branch, Center for Cancer Research National Cancer Institute, Mark O. Hatfield Clinical Research Center, Room 4-5330, 10 Center Drive, Bethesda, Maryland 20892-1457, USA. Tel: +1 301 402 2912; Fax: +1 301 402 1001; E-mail: jmorris@mail.nih.gov

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Abstract

Over the past decade, monoclonal antibodies have dramatically impacted the treatment of haematological malignancies, as evidenced by the effect of rituximab on the response rate and survival of patients with follicular and diffuse large B cell non-Hodgkin's lymphoma. Currently, only two monoclonal antibodies – the anti-CD33 immunotoxin gemtuzumab ozogamicin and the CD52-directed antibody alemtuzumab – are approved for treatment of relapsed acute myeloid leukaemia in older patients and B cell chronic lymphocytic leukaemia, respectively. Although not approved for such treatment, alemtuzumab is also active against T cell prolymphocytic leukaemia, cutaneous T cell lymphoma and Sézary syndrome, and adult T cell leukaemia and lymphoma. In addition, rituximab has demonstrated activity against B cell chronic lymphocytic and hairy cell leukaemia. Monoclonal antibodies targeting CD4, CD19, CD20, CD22, CD23, CD25, CD45, CD66 and CD122 are now being studied in the clinic for the treatment of leukaemia. Here, we discuss how these new antibodies have been engineered to reduce immunogenicity and improve antibody targeting and binding. Improved interactions with Fc receptors on immune effector cells can enhance destruction of target cells through antibody-dependent cellular cytotoxicity and complement-mediated cell lysis. The antibodies can also be armed with cellular toxins or radionuclides to enhance the destruction of leukaemia cells.

Type: Review Article
Information: Expert Reviews in Molecular Medicine , Volume 11 , July 2009 , e29

DOI: https://doi.org/10.1017/S1462399409001215 [Opens in a new window]
Copyright: Copyright © Cambridge University Press 2009

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Antibody-based therapy of leukaemia

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