TY - JOUR
T1 - Adenovirus tumor targeting and hepatic untargeting by a coxsackie/adenovirus receptor ectodomain anticarcinoembryonic antigen bispecific adapter
AU - Li, Hua Jung
AU - Everts, Maaike
AU - Pereboeva, Larisa
AU - Komarova, Svetlana
AU - Idan, Anat
AU - Curiel, David T.
AU - Herschman, Harvey R.
PY - 2007/6/1
Y1 - 2007/6/1
N2 - Adenovirus vectors have a number of advantages for gene therapy. However, because of their lack of tumor tropism and their preference for liver infection following systemic administration, they cannot be used for systemic attack on metastatic disease. Many epithelial tumors (e.g., colon, lung, and breast) express carcinoembryonic antigen (CEA). To block the natural hepatic tropism of adenovirus and to "retarget" the virus to CEA-expressing tumors, we used a bispecific adapter protein (sCAR-MFE), which fuses the ectodomain of the coxsackie/adenovirus receptor (sCAR) with a single-chain anti-CEA antibody (MFE-23). sCAR-MFE untargets adenovirus-directed luciferase transgene expression in the liver by >90% following systemic vector administration. Moreover, sCARMFE can "retarget" adenovirus to CEA-positive epithelial tumor cells in cell culture, in s.c. tumor grafts, and in hepatic tumor grafts. The sCAR-MFE bispecific adapter should, therefore, be a powerful agent to retarget adenovirus vectors to epithelial tumor metastases.
AB - Adenovirus vectors have a number of advantages for gene therapy. However, because of their lack of tumor tropism and their preference for liver infection following systemic administration, they cannot be used for systemic attack on metastatic disease. Many epithelial tumors (e.g., colon, lung, and breast) express carcinoembryonic antigen (CEA). To block the natural hepatic tropism of adenovirus and to "retarget" the virus to CEA-expressing tumors, we used a bispecific adapter protein (sCAR-MFE), which fuses the ectodomain of the coxsackie/adenovirus receptor (sCAR) with a single-chain anti-CEA antibody (MFE-23). sCAR-MFE untargets adenovirus-directed luciferase transgene expression in the liver by >90% following systemic vector administration. Moreover, sCARMFE can "retarget" adenovirus to CEA-positive epithelial tumor cells in cell culture, in s.c. tumor grafts, and in hepatic tumor grafts. The sCAR-MFE bispecific adapter should, therefore, be a powerful agent to retarget adenovirus vectors to epithelial tumor metastases.
UR - http://www.scopus.com/inward/record.url?scp=34347206848&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-06-4679
DO - 10.1158/0008-5472.CAN-06-4679
M3 - Article
C2 - 17545616
AN - SCOPUS:34347206848
SN - 0008-5472
VL - 67
SP - 5354
EP - 5361
JO - Cancer research
JF - Cancer research
IS - 11
ER -