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

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 lymphoma (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 established 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.

journal_name

Blood

journal_title

Blood

authors

Schliemann C,Palumbo A,Zuberbühler K,Villa A,Kaspar M,Trachsel E,Klapper W,Menssen HD,Neri D

doi

10.1182/blood-2008-05-160747

subject

Has Abstract

pub_date

2009-03-05 00:00:00

pages

2275-83

issue

10

eissn

0006-4971

issn

1528-0020

pii

blood-2008-05-160747

journal_volume

113

pub_type

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