4067 Background: SC-1 is a human monoclonal IgM antibody that targets CD55SC-1, a cell surface receptor specifically expressed on human GC cells, inducing apoptotic cell death and tumor cell regression in nude mice with no toxicity. The aim of this study was to examine whether CD55SC-1 expression is a prognostic tool in GC, and whether SC-1 confers a survival benefit in GC patients. METHODS Retrospective data from 126 CD55SC-1 positive and negative GC surgery-only patients from 1990-1997 was used to determine the prognostic ability of CD55SC-1. In an open-label, non-randomized study between 1997-2001, 51 CD55SC-1 positive GC patients received a single i.v. infusion of 10-30mg SC-1 24-48 hours before curative surgical (R0) resection. Data were compared to 19 CD55SC-1 negative GC patients who received only curative surgery between 1997-2001. RESULTS In the retrospective analysis, median survival of CD55SC-1 negative R0 patients was better than untreated CD55SC-1 positive R0 patients (93 months vs. 27 months); better UICC staging is associated with CD55SC-1 negative patients who are more associated with longer survival than CD55SC-1 positive patients (Cox proportional hazards, HR=2). In R0 resected patients after 1997, treatment with SC-1 increased survival at 2 years (77%) compared to CD55SC-1 negative untreated patients (63%). CONCLUSIONS CD55SC-1 may be a prognostic factor in GC; an imbalance in UICC stage between CD55SC-1 positive and negative patients requires further data to confirm the prognostic ability of CD55SC-1, and may also indicate that CD55SC-1positive tumors are more aggressive. Treatment of CD55SC-1 positive GC patients with SC-1 increased 2-year survival compared to CD55SC-1 negative untreated patients. [Table: see text].