Complement activation determines the therapeutic activity of rituximab in vivo

Nicola Di Gaetano, Elena Cittera, Rachele Nota, Annunciata Vecchi, Valeria Grieco, Eugenio Scanziani, Marina Botto, Martino Introna, Josée Golay

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Rituximab is an anti-CD20 chimeric mAb effective for the treatment of B-NHL. It can lyse lymphoma cells in vitro through both C- and Ab-dependent cellular cytotoxicity. The mechanism of action of rituximab in vivo is however still unclear. We have set up a new in vivo model in nonimmunodeficient mice by stable transduction of the human CD20 cDNA in the murine lymphoma line EL4. Animals injected i.v. with the EL4-CD20+ lymphoma cells died within 30 days with evident liver, spleen, and bone marrow involvement, confirmed by immunohistochemistry and PCR analysis. A single injection of rituximab or the murine anti-CD20 Ab 1F5, given i.p. 1 day after the tumor, cured 100% of the animals. Indeed, at week 4 after tumor cell inoculation, CD20+ cells were undetectable in all organs analyzed in rituximab-treated animals, as determined by immunohistochemistry and PCR. Rituximab had no direct effect on tumor growth in vitro. Depletion of either NK cells or neutrophils or both in tumor-injected animals did not affect the therapeutic activity of the drug. Similarly, rituximab was able to eradicate tumor cells in athymic nude mice, suggesting that its activity is T cell independent. In contrast, the protective activity of rituximab or the 1F5 Ab was completely abolished in syngeneic knockout animals lacking C1q, the first component of the classical pathway of C (C1qa-/-). These data demonstrate that C activation is fundamental for rituximab therapeutic activity in vivo.

Original languageEnglish
Pages (from-to)1581-1587
Number of pages7
JournalJournal of Immunology
Issue number3
Publication statusPublished - Aug 1 2003

ASJC Scopus subject areas

  • Immunology

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  • Cite this

    Di Gaetano, N., Cittera, E., Nota, R., Vecchi, A., Grieco, V., Scanziani, E., Botto, M., Introna, M., & Golay, J. (2003). Complement activation determines the therapeutic activity of rituximab in vivo. Journal of Immunology, 171(3), 1581-1587.