The antibody-mediated targeted delivery of cytokines to sites of disease is a promising avenue for cancer therapy, but it is largely unexplored for the treatment of chronic inflammatory conditions. Using both radioactive and fluorescent techniques, the human monoclonal antibodies L19 and G11 (specific to two markers of angiogenesis that are virtually undetectable in normal adult tissues) were f...

Current imaging modalities of human atherosclerosis, such as angiography, ultrasound, and computed tomography, visualize plaque morphology. However, methods that provide insight into plaque biology using molecular tools are still insufficient. The extra-domain B (ED-B) is inserted into the fibronectin molecule by alternative splicing during angiogenesis and tissue remodeling but is virtually un...

BACKGROUND Ligand-targeted approaches have proven successful in improving the therapeutic index of a number of drugs. We hypothesized that the specific targeting of TNF-alpha antagonists to inflamed tissues could increase drug efficacy and reduce side effects. RESULTS Using uteroglobin (UG), a potent anti-inflammatory protein, as a scaffold, we prepared a bispecific tetravalent molecule consi...

BACKGROUND The antibody-based targeted delivery of bioactive molecules to tumour vasculature is an attractive avenue to concentrate therapeutic agents at cancer sites, while sparing normal organs. L19, F8 and F16 are three fully human monoclonal antibodies, specific to splice isoforms of fibronectin and tenascin-C, which bind to sites of active tissue remodeling and which are currently in Phase...

Wherever there is cancer, there will be blood and blood vessels to support tumor growth. While the majority of anticancer drugs are designed to directly kill tumor cells, recent strategies are focusing on drugs that indirectly kill cancer cells by targeting the tumor microenvironment and tumor vasculature. This strategy gained a significant boost with the approval of the angiogenesis inhibitor ...

PURPOSE Extra domain B (ED-B) fibronectin is a specific tumor matrix marker for targeting angiogenesis in solid tumors. In this study, the radiotherapeutic potential of the directly radioiodinated divalent anti-ED-B antibody fragment, L19 small immunoprotein (L19-SIP; 75,000 Da), was compared with a pretargeting approach using the bispecific antibody AP39xm679 (bsMAb; 75,000 Da). EXPERIMENTAL...

1 2 3 4 5 6 7 8 1 e0 e9 e11 e12 e10 e7 e15 2 e4 e2 e5 e6 L L L e13 3 e1 e3 e8 L L L L e16 4 L L L L L L e17 5 e0 e11 e12 e10 e9 L e15 6 e4 e2 e6 L19 e7 e5 L20 e13 7 e1 e3 L24 e8 L23 L22 e16 8 L25 L26 L30 L27 L28 L29 e17 9 e0 e12 e10 L31 e11 e9 e15 10 e4 e2 L19 L20 e6 e7 e13 11 e1 e3 L22 L23 L24 e8 e16 12 L L25 L26 L29 L30 L27 L28 e17 13 e0 e10 L21 e12 e9 e11 e15 14 e4 e2 e7 e6 L20 L19 e13 15 e1...

PURPOSE Radiotherapy modifies the tumor microenvironment and causes the release of tumor antigens, which can enhance the effect of immunotherapy. L19 targets the extra domain B (ED-B) of fibronectin, a marker for tumor neoangiogenesis, and can be used as immunocytokine when coupled to IL2. We hypothesize that radiotherapy in combination with L19-IL2 provides an enhanced antitumor effect, which ...

The erbB-2 (or HER-2 or neu) gene is amplified and overexpressed in approximately one-third of cancers of the breast, stomach, and ovary. Evidence is accumulating that erbB-2 overexpression is associated with decreased survival of breast cancer patients. In an effort to understand how erbB-2 overexpression might impart a more malignant potential to breast cancer cells, we have searched for evid...

Angiogenesis is a characteristic feature of many aggressive tumors and of other relevant disorders. Molecules capable of specifically binding to new-forming blood vessels, but not to mature vessels, could be used as selective vehicles and would, therefore, open diagnostic and therapeutic opportunities. We have studied the distribution of the ED-B oncofetal domain of fibronectin, a marker of ang...