Impact of Polymorphisms on the Clinical Outcomes of Monoclonal Antibody Therapy Against Hematologic Malignancies

  • Dong Hwan Kim
Part of the Cancer Drug Discovery and Development™ book series (CDD&D)


Monoclonal antibodies that target various specific antigens can be used to kill the tumor cells expressing specific antigens, especially in hematologic cancers. Rituximab, one of the commonly used monoclonal antibodies, was suggested to mediate its action mechanism via antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), or a direct pro-apoptotic effect. It has been proposed that the inter-individual variation of gene expression is a consequence of single nucleotide polymorphisms (SNPs) and that the response to a monoclonal antibody can be affected by the SNPs in the host genes corresponding to the drug binding to the target cells or the metabolism of the drug.

This chapter reviews the current understanding of the mechanism of action of monoclonal antibodies (especially rituximab), the role of Fcγ receptor and Fcγ receptor gene polymorphisms, and their impact on treatment outcomes in hematologic malignancies including follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Waldenstrom’s macroglobulinemia (WM), and chronic lymphocytic leukemia (CLL). In addition, we discuss the approaches augmenting its clinical activity, especially focusing on Fcγ receptor re-engineered monoclonal antibody.

Key Words

Polymorphisms monoclonal antibody hematologic malignancies rituximab 


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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Dong Hwan Kim
    • 1
  1. 1.Dept. of Hematology/OncologySamsung Medical Center, Sungkyunkwan University School of MedicineSeoulKorea

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