Ovarian cancer has features that makes it well-suited for MAb adjuvant
immunotherapy. Several of the MAbs used in clinical trials mediate ca
ncer cell destruction by activation of complement (C), In this study,
therefore, we examined the ability of ovarian-tumor cells to resist C
attack. We found that the C regulators membrane cofactor protein (MCP,
CD46) and protectin (CD59) were strongly expressed in the tumor cells
in all 28 benign and malignant tumors examined. Decay-accelerating fa
ctor (DAF; CD55) was more heterogeneously expressed, and only 75% of t
he tumors exhibited a moderate amount of DAF in the tumor cells. In ad
enoma cells, CD59 and DAF were preferentially located apically, while
in adenocarcinoma cells they were expressed also at the basolateral ce
ll surface, The ovarian-carcinoma cell lines SK-OV-3, Caov-3, SW626 an
d PA-I expressed both the 58- and the 68-kDa isoforms of MCP. DAF was
present as a glycosyl-phosphatidylinositol(GP I)-anchored 70-kDa glyco
protein, The surface-expression level of DAF varied, and correlated wi
th the vulnerability of the cells to C-mediated lysis. CD59 was expres
sed as a GPI-linked 19- to 25-kDa protein exhibiting multiple glycosyl
ation variants. The surface expression of CD59 correlated with the amo
unt of the main 1.9 + 2.1-kb CD59 mRNA transcripts. Neutralization of
CD59 with an anti-CD59 MAb significantly enhanced C-mediated killing o
f the cell lines. Low expression of C regulators on the PA-I teratocar
cinoma cell line was associated with high sensitivity to C lysis. Thus
, the expression of C regulators on malignant ovarian cells may consti
tute a tumor escape mechanism, and is a critical parameter to be exami
ned when MAb therapy is being considered. (C) 1997 Wiley-Liss, Inc.