S. Narisawa et al., TRANSGENIC MICE EXPRESSING THE TUMOR-MARKER GERM-CELL ALKALINE-PHOSPHATASE - AN INVIVO TUMOR-MODEL FOR HUMAN CANCER ANTIGENS, Proceedings of the National Academy of Sciences of the United Statesof America, 90(11), 1993, pp. 5081-5085
We have generated a series of transgenic mouse lines harboring the ent
ire human germ cell alkaline phosphatase (GCAP) gene linked to progres
sively longer sequences of flanking DNA. A 450-bp promoter sequence di
rects the expression of GCAP to the intestine and endothelial cells, w
hile a 5' sequence of 1.7 kb directs GCAP expression to the spermatoge
nic lineage and to the eight-cell through the blastocyst stage of prei
mplantation development. The expression of GCAP in these FVB/N transge
nic mice induces a cellular immune tolerance to GCAP. When mouse fibro
sarcoma MO4 cells (C3H derived), stably transfected with the cloned GC
AP gene, were injected s.c. in nontransgenic control (C3Hx FVB/N) hybr
id mice, GCAP-positive tumor cells were rejected. However, when GCAP-e
xpressing transgenic (C3HxFVB/N) hybrid mice were challenged with thes
e cells, GCAP-positive tumors developed. Tumors also developed in the
transgenic hybrid mice upon injection of MO4 cells transfected with th
e highly homologous placental alkaline phosphatase (PLAP) cDNA in spit
e of the presence in PLAP of 10 amino acids that are different from th
e corresponding residues in GCAP. These GCAP transgenic mice will allo
w the study of the immune response associated with the repeated admini
stration of conjugated or derivatized anti-GCAP and anti-PLAP monoclon
al antibodies. They will also enable evaluation of the therapeutic pot
ential of bifunctional antibodies for T-cell recruitment and destructi
on of GCAP/PLAP-producing tumor cells.