dodekin

A human antibody-cytokine fusion protein composed of the recombinant form of the endogenous immunostimulatory cytokine interleukin-12 (IL-12) fused, in tandem diabody format, to the N-terminus of the human monoclonal antibody L19 specific for the extra-domain B of fibronectin (ED-B), with potential immunostimulating and antineoplastic activities. Upon administration, the antibody moiety of dodekin targets and binds to fibronectin-expressing cells in the tumor vasculature, thereby delivering IL-12 directly to the tumor vasculature. In turn, the IL-12 moiety targets, binds to and activates its cell-surface receptor, and activate the immune system by promoting the activation of natural killer cells (NKs), inducing secretion of interferon-gamma (IFN-g) and promoting cytotoxic T-lymphocyte (CTL) responses against tumor cells. This may result in immune-mediated tumor cell death, inhibition of tumor cell proliferation and inhibition of tumor angiogenesis. ED-B of fibronectin, a naturally occurring marker of tissue remodeling and angiogenesis, is over-expressed in the extracellular matrix and blood vessels of a majority of aggressive solid human tumors. It is not detectable in normal vessels and tissues.