Gangliosides as targets for immunotherapy for pancreatic Adenocarcinoma

BACKGROUND, Pancreatic adenocarcinoma cells express gangliosides and sialyl Lewis (sLe) antigens. It is not known whether these carbohydrate antigens can be targeted by immunotherapy. The authors measured the expression of GM (2) and sLe antigens on the surface of pancreatic carcinoma cells and the s erum levels of total gangliosides, GM(2), and antiganglioside antibodies in patients with pancreatic carcinoma. METHODS, Cell surface GM(2) and sLe antigens were measured by cell suspensi on enzyme linked immunoadsorbent assay (ELISA) in four pancreatic carcinoma cell lines. Sera from 20 pancreatic carcinoma patients and 20 age- and gen der-matched healthy volunteers were analyzed for antiganglioside and anti-a le immunoglobulin (Ig) M titers by ELISA. Serum levels of total ganglioside s and GM(2) also were measured. RESULTS. All cell lines expressed GM(2) and sLe antigens. When compared wit h age- and gender-matched volunteers, patients had significantly higher ser um levels of total gangliosides (25.6 +/- 9.0 mg/dL vs. 15.6 +/- 2.7 mg/dL; P < 0.001), GM(2) (0.278 +/- 0.425 mg/dL vs. 0.013 +/- 0.018 mg/dL; P = 0. 02), ELISA units of anti-GM(2) IgM antibody (368 +/- 95 vs. 155 +/- 25; P = 0.04) and anti-GD(1b) IgM antibody (351 +/- 91 vs. 138 +/- 26; P = 0.03), but not anti-sLe(x) IgM (1389 +/- 345 vs. 1081 +/- 224; P = 0.46) or anti-s Le(a) IgM antibody (1097 +/- 253 vs. 1200 +/- 315; P = 0.80). Patients with unresectable tumors had higher serum levels of total gangliosides compared with patients with resectable tumors, and a serum level > 25 mg/dL was fou nd to correlate significantly with poor overall survival (P < 0.02). CONCLUSIONS. Increased serum levels of total gangliosides and GM(2) may ref lect shedding or release of gangliosides from the surface of tumor cells. P roduction of IgM antibody against GM(2) and GD(1b) indicates that these gan gliosides are immunogenic antigens that may be potential targets for effect ive active immunotherapy. Cancer 2000;88:1828-36. (C) 2000 American Cancer Society.