209 ISSN 1475-0708 10.2217/THY.10.19 © 2010 Future Medicine Ltd Therapy (2010) 7(3), 209–212 E ditorial Therapy (2010) 7(3), 209–212 “…carefully designed screening strategies of recombinant antbody libraries have the potental to lead to the identfcaton of ideal targetng reagents for both in vitro and in vivo uses.” Nathalie Scholler Department of Obstetrics & Gynecology, Center for Research on Reproducton & Women’s Health, Penn Ovarian Cancer Research Center, University of Pennsylvania, Philadelphia, PA 19104-6160, USA Tel.: +1 215 898 0164 Fax: +1 215 573 5129 naths@mail.med.upenn.edu 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 intracellular localization of the macromolecules can be con- trolled by coupling them to cell-penetrating peptides and transduction domains [15,16] , while sensitivity and specifcity can be increased by strategies such as attachment to proteins and particles, encapsulation into micelles and caged structures, biochemical reporters that are sensi- tive to pH, proteins, temperature or oxygen [17] , and targeting to receptors. The conjugation of targeting platforms to nanoparticles optimizes specifc local delivery. Any moiety with specifc binding properties, such as monoclonal anti- bodies [18] , or molecules that target cell recep- tors [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 specifcally bind to a unique antifolate receptor while folate binds to any folate receptors, the exquisite epitope recognition of antibody conceptually guaran- tees a much higher specifcity than natural mol- ecules. 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 organ- isms 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 detec- tion of ovarian cancer has been approved to date. Almost 30 years after the discovery of CA125 [1] , ovarian cancer continues to be generally diag- nosed at an advanced stage where the case:fatality ratio is high, thus remaining the most lethal of all gynecologic malignancies among US women. Attempts at screening with conventional imaging strategies have been hampered by high levels of false-positives with only 13–21% of the women that undergo surgery to remove adnexal masses actually having ovarian cancer [2] . As a result, while the case for early detection of ovarian can- cer is undeniable [3] , the current opinions regard- ing screening for ovarian cancer in the general population are divided between negative [4–6] and mildly positive [7,8] recommendations that emphasize stable markers in healthy controls over time. Clearly, to become a standard-of-care screening, modalities must be improved, but doubts about the achievability of the task haunt the feld. When necessary to defy apparently grim probabilities, the quote of my compatriots, “Impossible n’est pas français,” naturally comes to mind. (“Impossible n’est pas français” can be translated in English as “There is no such word as can’t”. This sentence attributed to Napoleon is actually a pun meaning both ‘impossible is not French’ and ‘impossible is not idiomatically cor- rect’.) Indeed, with the accelerated development of targeted macromolecules engineered for cargo delivery, early diagnosis and therapy of ovarian cancer now appear as a tangible future. Macromolecules preferentially accumulate in tumors due to the enhanced permeability and retention effect that arises from the dif- ference in clearance rate between solid tumors and normal tissues [9] . Various imaging and therapeutic reagents or reporters for molecular and functional imaging studies, ranging from For reprint orders, please contact: reprints@futuremedicine.com