Nonfucosylated anti-CD20 antibody potentially induces apoptosis in lymphoma cells through enhanced interaction with FcgammaRIIIb on neutrophils

Leuk Res. 2010 May;34(5):666-71. doi: 10.1016/j.leukres.2009.10.029.

Abstract

We demonstrate herein the augmentation of rituximab-mediated apoptosis in lymphoma cell lines by cross-linking with recombinant FcgammaRs, which is further enhanced by using a nonfucosylated variant of rituximab having strong FcgammaRIII-binding capacity. Furthermore, we show that neutrophils can serve as physiological cross-linkers that augment anti-CD20-mediated apoptosis, as evidenced by (i) the neutrophil-augmented apoptosis was more profound for the nonfucosylated variant of rituximab and (ii) the mechanism depended on FcgammaRIIIb but not on FcgammaRIIa. Taken together, we suggest a potential anti-tumour mechanism of nonfucosylated anti-CD20 antibody by which antibody molecules are cross-linked through enhanced interaction with FcgammaRIIIb in neutrophils.

MeSH terms

  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Murine-Derived
  • Antibody-Dependent Cell Cytotoxicity / drug effects
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / immunology
  • Cell Line, Tumor
  • Cross-Linking Reagents
  • Humans
  • Lymphoma / immunology*
  • Neutrophils / drug effects*
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Receptors, IgG / immunology
  • Receptors, IgG / metabolism*
  • Rituximab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents
  • Cross-Linking Reagents
  • FCGR2B protein, human
  • Receptors, IgG
  • Rituximab