Comparative immunohistochemical staining of atherosclerotic plaques using F16, F8 and L19: Three clinical-grade fully human antibodies

The antibody‐based targeted delivery of interleukin‐4 and 12 to the tumor neovasculature eradicates tumors in three mouse models of cancer

“…These clinical development activities are supported by the fact that the F8 antibody recognizes the human and murine cognate antigen with identical affinity, and by the observation that the EDA domain of fibronectin is strongly expressed in a variety of different malignancies. 11,12,[48][49][50] The therapeutic potential of F8-IL4 may deserve to be explored also in nononcological conditions. While the EDA domain of fibronectin is virtually undetectable in most normal adult tissues (with the exception of the female reproductive system), the F8 antibody has been shown to efficiently target endometriosis 8 and atherosclerosis 49 in vivo.…”

“…11,12,[48][49][50] The therapeutic potential of F8-IL4 may deserve to be explored also in nononcological conditions. While the EDA domain of fibronectin is virtually undetectable in most normal adult tissues (with the exception of the female reproductive system), the F8 antibody has been shown to efficiently target endometriosis 8 and atherosclerosis 49 in vivo. Therapy studies with F8-IL4 in angiogenesis-related chronic inflammatory diseases will be important not only to assess the activity of the product against these conditions, but also to learn about its safety profile in polymorbid patients (e.g., elderly patients).…”

Mechanoresponsive Networks Controlling Vascular Inflammation

“…26 Therefore, both ROS and focal adhesion kinase signaling events are essential for nuclear translocation and transcriptional activity of NF-κB in response to acute flow. Although it has been shown that the content of extracellular matrix differs between atheroprone (fibronectin-rich) 27 and atheroprotected (collagen-rich) regions, 28 disturbed flow in combination with intergrin-fibronectin interaction is required for sustained NF-κB and JNK activation.. 29,30 Furthermore, a signaling pathway involving the adaptor protein Shc has been suggested as the molecular switch that coordinates interaction between cell-cell and cell-extracellular matrix, resulting in the initial extracellular matrix-independent activation of extracellular-signal-regulated kinase (ERK) on acute onset of flow to follow by extracellular matrix-dependent NF-κB activation. 31 Physiological mechanics are complex, and arterial WSS varies in terms of magnitude, direction, spatial gradient, and frequency.…”

Antibody-based delivery of IL4 to the neovasculature cures mice with arthritis

“…Thanks to advanced technologies (9), high-affinity human antibodies can be raised against virtually any accessible marker of disease and may selectively accumulate at the site of disease, thus facilitating the development of pharmacodelivery strategies. In particular, the F8 antibody, specific to the alternatively spliced extra domain A (EDA) of fibronectin, a marker of angiogenesis, has been shown to strongly react with neovascular structures at sites of chronic inflammation in human specimens and in the mouse (7,10,11), whereas the antigen is only found in placenta, endometrium, and some vessels of the ovaries in normal adult tissue (7). The immunocytokine F8-IL10 is currently being investigated in clinical trials in patients with active RA (12).…”