Expression of the oncofetal ED-B–containing fibronectin isoform in hematologic tumors enables ED-B–targeted 131I-L19SIP radioimmunotherapy in Hodgkin lymphoma patients
- 5 March 2009
- journal article
- Published by American Society of Hematology in Blood
- Vol. 113 (10), 2265-2274
- https://doi.org/10.1182/blood-2008-06-160416
Abstract
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.Keywords
This publication has 36 references indexed in Scilit:
- Multiple cardiovascular defects caused by the absence of alternatively spliced segments of fibronectinDevelopmental Biology, 2007
- Vascular update: Morphogenesis, tumors, malformations, and molecular dimensionsAmerican Journal of Medical Genetics Part A, 2006
- Fibronectin on activated T lymphocytes is bound to gangliosides and is present in detergent insoluble microdomainsImmunology & Cell Biology, 2005
- Expression of extradomain-B–containing fibronectin in subretinal choroidal neovascular membranesAmerican Journal of Ophthalmology, 2003
- Fibronectin synthesis by activated T lymphocytes: up‐regulation of asurface‐associated isoform with signalling functionImmunology, 2000
- Antibody specific for extra domain B of fibronectin demonstrates elevated levels of both extra domain B(+) and B(-) fibronectin in osteoarthritic canine cartilageMatrix Biology, 1995
- Expression of the Alternatively Spliced EIIIB Segment of FibronectinCell Adhesion and Communication, 1995
- Reappearance of an embryonic pattern of fibronectin splicing during wound healing in the adult rat.The Journal of cell biology, 1989
- FIBRONECTIN AND ITS RECEPTORSAnnual Review of Biochemistry, 1988
- Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes).Journal of Histochemistry & Cytochemistry, 1984