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 Blood, 5 March 2009, Vol. 113, No. 10, pp. 2265-2274.
Prepublished online as a Blood First Edition Paper on January 8, 2009; DOI 10.1182/blood-2008-06-160416.

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LYMPHOID NEOPLASIA

Expression of the oncofetal ED-B–containing fibronectin isoform in hematologic tumors enables ED-B–targeted 131I-L19SIP radioimmunotherapy in Hodgkin lymphoma patients

Stefanie Sauer1,*, Paola A. Erba2,*, Mario Petrini3, Andreas Menrad4, Leonardo Giovannoni5, Chiara Grana6, Burkhard Hirsch1, Luciano Zardi7, Giovanni Paganelli6, Giuliano Mariani2, Dario Neri8, Horst Dürkop1,{dagger}, and Hans D. Menssen9,{dagger}

1 Department of Pathology, Campus Benjamin Franklin, Charité-Universitätsmedizin, Berlin, Germany; 2 Regional Center of Nuclear Medicine and 3 Department of Hematology, University of Pisa Medical School, Pisa, Italy; 4 Genzyme Europe Research, Cambridge Science Park, Cambridge, United Kingdom; 5 Philogen SpA, Siena, Italy; 6 Department of Nuclear Medicine, European Institute of Oncology, Milan, Italy; 7 Laboratory of Innovative Therapies, Centro Biotecnologie Avanzate, Genova, Italy; 8 Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland; and 9 Department of Global Clinical Development Oncology, Bayer HealthCare Pharmaceuticals, Montville, NJ

Current treatment of hematologic malignancies involves rather unspecific chemotherapy, frequently resulting in severe adverse events. Thus, modern clinical research focuses on compounds able to discriminate malignant from normal tissues. Being expressed in newly formed blood vessels of solid cancers but not in normal mature tissues, the extradomain B of fibronectin (ED-B FN) is a promising target for selective cancer therapies. Using immunohistology with a new epitope retrieval technique for paraffin-embedded tissues, ED-B FN expression was found in biopsies from more than 200 Hodgkin and non-Hodgkin lymphoma patients of nearly all entities, and in patients with myeloproliferative diseases. ED-B FN expression was nearly absent in normal lymph nodes (n = 10) and bone marrow biopsies (n = 9). The extent of vascular ED-B FN expression in lymphoma tissues was positively correlated with grade of malignancy. ED-B FN expression was enhanced in lymph nodes with severe lymphadenopathy and in some hyperplastic tonsils. The in vivo accessibility of ED-B FN was confirmed in 3 lymphoma patients, in whom the lymphoma lesions were visualized on scintigraphy with 131I-labeled L19 small immunoprotein (131I-L19SIP). In 2 relapsed Hodgkin lymphoma patients131I-L19SIP radioimmunotherapy induced a sustained partial response, qualifying ED-B FN as a promising target for antibody-based lymphoma therapies.


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