Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 102, Issue 1, Pages 75-85Publisher
WILEY
DOI: 10.1002/ijc.10662
Keywords
antibody formats; tumor vasculature; tumor targeting; clinical applications; cancer diagnosis and therapy
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We recently demonstrated that a human recombinant scFv, L19, reacting with the ED-B domain of fibronectin, a marker of angiogenesis, selectively targets tumoral vasculature in vivo. Using the variable regions of L19, we constructed and expressed a human small immunoprotein (SIP) and a complete human 1gG1 and performed biodistribution studies in tumor-bearing mice to compare the blood clearance rate, in vivo stability and performance in tumor targeting of the 3 L19 formats [dimeric scFv (scFV)(2), SIP and 1gG1]. The accumulation of the different antibody formats in the tumors studied was a consequence of the clearance rate and in vivo stability of the molecules. Using the SIP, the %ID/g in tumors was 2-5 times higher than that of the (scFV)2, reaching a maximum 4-6 hr after injection. By contrast, the accumulation of 1gG1 in tumors constantly rose during the experiments. However, due to its slow clearance, the tumor-blood ratio of the %ID/g after 144 hr was only about 3 compared to a ratio of 10 for the (scFV)2 and 70 for the SIP after the same period of time. The different in vivo behavior of these 3 completely human L19 formats could be exploited for different diagnostic and/or therapeutic purposes, depending on clinical needs and disease. Furthermore, the fact that ED-B is 100% homologous in human and mouse, which ensures that L19 reacts equally well with the human and the murine antigen, should expedite the transfer of these reagents to clinical trials. (C) 2002 Wiley-Liss, Inc.
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