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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.
Previous Article | Next Article 
Submitted June 2, 2008
Accepted December 11, 2008
Expression of the oncofetal ED-B containing fibronectin isoform in hematologic tumors enables ED-B targeted 131I-L19SIP radioimmunotherapy in Hodgkin lymphoma patients
Stefanie Sauer, Paola A. Erba, Mario Petrini, Andreas Menrad, Leonardo Giovannoni, Chiara Grana, Burkhard Hirsch, Luciano Zardi, Giovanni Paganelli, Giuliano Mariani, Dario Neri, Horst Durkop, and Hans D. Menssen*
Department of Pathology, Campus Benjamin Franklin, Charite-Universitatsmedizin, Berlin, Germany
Regional Center of Nuclear Medicine, University of Pisa Medical School, Pisa, Italy
Department of Hematology, University of Pisa Medical School, Pisa, Italy
Genzyme Europe Research, Cambridge Science Park, Cambridge, United Kingdom
Philogen, SpA, Siena, Italy
Department of Nuclear Medicine, European Institute of Oncology, Milan, Italy
Laboratory of Innovative Therapies, Centro Biotecnologie Avanzate, Genoa, Italy
Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, Zurich, Switzerland
Department of Global Clinical Development Oncology, Bayer HealthCare Pharmaceuticals, Montville, NJ, United States
* Corresponding author; email: hansdietrich.menssen{at}bayer.com.
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 extra-domain 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 three lymphoma patients, in whom the lymphoma lesions were visualized on scintigraphy with 131I-labeled L19 small immunoprotein (131I-L19SIP). In two relapsed Hodgkin lymphoma patients, 131I-L19SIP radioimmunotherapy induced a sustained partial response, qualifying ED-B FN as a promising target for antibody-based lymphoma therapies.

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