Clinical evidence of efficient tumor targeting based on single-chain Fv antibody selected from a combinatorial library

被引:216
作者
Begent, RHJ
Verhaar, MJ
Chester, KA
Casey, JL
Green, AJ
Napier, MP
HopeStone, LD
Cushen, N
Keep, PA
Johnson, CJ
Hawkins, RE
Hilson, AJW
Robson, L
机构
[1] CTR PROTEIN ENGN,CRC PHASE TRAILS COMM 3,CAMBRIDGE CP2 2QH,ENGLAND
[2] CTR PROTEIN ENGN,CRC PHASE TRAILS COMM 3,CAMBRIDGE CP2 2QH,ENGLAND
关键词
D O I
10.1038/nm0996-979
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We present a system for cancer targeting based on single-chain Fv (scFv) antibodies selected from combinatorial libraries, produced in bacteria and purified by using an engineered tag. Combinatorial libraries of scFv genes contain great diversity, and scFv antibodies with characteristics optimized for a particular task can be selected from them using filamentous bacteriophage. We illustrate the benefits of this system by imaging patients with carcinoembryonic antigen (CEA)-producing cancers using an iodine-123 labeled scFv anti-CEA selected for high affinity. All known tumor deposits were located, and advantages over current imaging technology are illustrated. ScFvs are produced in a cloned form and can be readily engineered to have localizing and therapeutic functions that will be applicable in cancer and other diseases.
引用
收藏
页码:979 / 984
页数:6
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