Complete eradication of human B-cell lymphoma xenografts using rituximab in combination with the immunocytokine L19-IL2

Christoph Schliemann, Alessandro Palumbo, Kathrin Zuberbühler, Alessandra Villa, Manuela Kaspar, Eveline Trachsel, Wolfram Klapper, Hans Dietrich Menssen, Dario Neri

Research output: Contribution to journalArticle

Abstract

The antibody-mediated delivery of therapeutic agents to sites of angiogenesis is an attractive strategy for anticancer therapy, but is largely unexplored in hematologic malignancies. In the present study, we show that the extra domain B (EDB) of fibronectin, a marker of angiogenesis, is expressed in B-cell non-Hodgkin lym-phoma (NHL) and that the human monoclonal anti-EDB antibody L19 can selectively localize to the lymphoma-associated subendothelial extracellular matrix. In vivo, the preferential accumulation of the antibody at the tumor site was confirmed by quantitative biodistribution analyses with radioiodinated antibody preparations. The fusion protein L19-IL2, which mediates the delivery of interleukin-2 (IL-2) to the neovasculature, displayed a superior antilymphoma activity compared with unconjugated IL-2 in localized and systemic xenograft models of NHL. When coadministered with rituximab, L19-IL2 induced complete remissions of estab-lished localized lymphomas and provided long-lasting protection from disseminated lymphoma. The combined use of rituximab and L19-IL2, which dramatically increases the infiltration of immune effector cells in lymphomas, may deserve clinical investigations, facilitated by the fact that L19-IL2 is currently being studied in phase II clinical trials in patients with solid tumors. (Blood. 2009;113:2275-2283)

Original languageEnglish
Pages (from-to)2275-2283
Number of pages9
JournalBlood
Volume113
Issue number10
DOIs
Publication statusPublished - Mar 5 2009

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ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Schliemann, C., Palumbo, A., Zuberbühler, K., Villa, A., Kaspar, M., Trachsel, E., Klapper, W., Menssen, H. D., & Neri, D. (2009). Complete eradication of human B-cell lymphoma xenografts using rituximab in combination with the immunocytokine L19-IL2. Blood, 113(10), 2275-2283. https://doi.org/10.1182/blood-2008-05-160747