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 serum 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 suspension enzyme linked immunoadsorbent assay (ELISA) in four pancreatic carcinoma cell lines. Sera from 20 pancreatic carcinoma patients and 20 age- and gender-matched healthy volunteers were analyzed for antiganglioside and anti-sLe immunoglobulin (Ig) M titers by ELISA. Serum levels of total gangliosides and GM(2) also were measured.


RESULTS
All cell lines expressed GM(2) and sLe antigens. When compared with age- and gender-matched volunteers, patients had significantly higher serum levels of total gangliosides (25.6 +/- 9.0 mg/dL vs. 15.6 +/- 2.7 mg/dL; P < 0.001), GM(2) (0.278 +/- 0.415 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-sLe(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 found to correlate significantly with poor overall survival (P < 0.02).


CONCLUSIONS
Increased serum levels of total gangliosides and GM(2) may reflect shedding or release of gangliosides from the surface of tumor cells. Production of IgM antibody against GM(2) and GD(1b) indicates that these gangliosides are immunogenic antigens that may be potential targets for effective active immunotherapy.
Chu
K U
KU
Roy E. Coats Research Laboratories and the Sonya Valley Ghidossi Vaccine Laboratory of the John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA, USA.
Ravindranath
M H
MH
Gonzales
A
A
Nishimoto
K
K
Tam
W Y
WY
Soh
D
D
Bilchik
A
A
Katopodis
N
N
Morton
D L
DL
D000230:Adenocarcinoma / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005678:G(M2) Ganglioside / Q000097:blood* / Q000276:immunology; D005732:Gangliosides / Q000097:blood* / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000032:analysis; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D014407:Tumor Cells, Cultured
D005732:Gangliosides; D007075:Immunoglobulin M; D005678:G(M2) Ganglioside