Gw. Cao et al., Analysis of the human carcinoembryonic antigen promoter core region in colorectal carcinoma-selective cytosine deaminase gene therapy, CANC GENE T, 6(6), 1999, pp. 572-580
We isolated a 204-base pair carcinoembryonic antigen (CEA) promoter core re
gion from a CEA-producing human colorectal carcinoma (CRC) and constructed
retrovirus vectors carrying the expression cassette consisting of the CEA p
romoter core region and the cytosine deaminase (CD) gene. pCD2 retrovirus c
arrying the CD gene directed by the retrovirus long terminal repeat promote
r served as a control vector. An in vitro study showed that the CEA promote
r conferred CEA-producing cell-selective CD expression, specifically when t
he CD expression cassette was inserted into the 3' long terminal repeat of
the retrovirus vector. CD-modified CRC xenografts in nude mice were sensiti
ve to 5-fluorocytosine and caused a profound bystander effect on the unmodi
fied CRC. When nude mice harboring intraperitoneally disseminated CRCs were
injected intraperitoneally with the CD expression cassette-carrying retrov
irus-producing cells, CD transduction into the disseminated CRCs and bone m
arrow (BM) was observed. CD expression was, however, restricted to CRCs, an
d it was observed in both CRCs and BM of mice injected with pCD2 retrovirus
-producing cells, resulting in better therapeutic outcomes without BM suppr
ession. These results indicate that effective and safe in vivo gene therapy
for CRC may be feasible by transferring the CD gene controlled by the CEA
promoter core region.