Novel targeting strategies using recombinant antibodies for early diagnosis and therapy of€ovarian cancer

" …carefully designed screening strategies of recombinant antibody libraries have the potential to lead to the identification of ideal targeting reagents for both in vitro and in vivo uses. " Novel targeting strategies using recombinant antibodies for early diagnosis and therapy of ovarian cancer lipid-based or paramagnetic nanoparticles to highly versatile polymers and viral capsids, can be used to detect and characterize pathological abnormalities [10–14]. The extra-or intra cellular localization of the macromolecules can be controlled by coupling them to cell-penetrating peptides and transduction domains [15,16], while sensitivity and specificity can be increased by strategies such as attachment to proteins and particles, encapsulation into micelles and caged structures, biochemical reporters that are sensitive to pH, proteins, temperature or oxygen [17], and targeting to receptors. The conjugation of targeting platforms to nanoparticles optimizes specific local delivery. Any moiety with specific binding properties, such as monoclonal anti-bodies [18], or molecules that target cell receptors [19–21] can be used as targeting reagents. For example, the folate receptor-a that is highly expressed by ovarian cancer cells can be targeted by folate or by an antifolate receptor-a antibody. Yet, since antibodies can specifically bind to a unique antifolate receptor while folate binds to any folate receptors, the exquisite epitope recog nition of antibody conceptually guarantees a much higher specificity than natural molecules. However, multiple hurdles – for which cost and time are not the least factors – exist on the road of production of monoclonal antibodies tolerated by the human immune system. Even if technical obstacles can be overcome given enough time and work, impediments linked to the immunization process cannot. Antibodies are naturally produced by organisms in contact with foreign and immunogenic molecules, two characteristics that most tumor-associated antigens lack. Tumor-associated anti-gens are mainly endogenous molecules over-expressed by tumors rather than being tumor specific, and are often conserved between humans and animals used for immunization. In addition, the ideal epitopes for in vivo targeting cell-surfaced, overexpressed molecules are most Despite major efforts to identify biomarkers or biomarker panels performing better than CA125, which is the most studied ovarian cancer bio-marker, no diagnostic marker for the early detection of ovarian cancer has been approved to date. Almost 30 years after the discovery of CA125 [1], ovarian cancer continues to be generally diagnosed at an advanced stage where the case:fatality ratio is high, thus remaining the most lethal of all gynecologic malignancies among US women. Attempts …