Endothelial-selectin ligands sialyl Lewis(x) and sialyl Lewis(a) are differentiation antigens immunogenic in human melanoma.
BACKGROUND
Sialyl Lewis(x) (sLe(x)) and sialyl Lewis(a) (sLe(a)), the endothelial-selectin ligands involved in extravasation of neutrophils and carcinomas, have been identified in human melanoma. This study explored the following issue: If these ligands are immunogenic tumor-differentiation antigens, they would be potential targets for immunotherapy because of their putative roles in extravasation and metastasis.


METHODS
Using a cell-suspension enzyme-linked immunosorbent assay (ELISA), the expression of sLe(x) and sLe(a) on the surface of normal melanocytes, melanoma cells from biopsies, and cell lines (M10-v, M24, and M101) constituting melanoma cell vaccine (MCV) were quantitated. Melanoma patients were immunized with the MCV expressing these antigens. Sera of normal individuals, sera of patients, and sera that adsorbed to sLe(x) and sLe(a) were titrated for anti-sLe antibodies by ELISA to verify the immunogenicity of the ligands.


RESULTS
The normal melanocytes did not express sLe(x) and poorly expressed sLe(a). Melanoma cells from tumor biopsies and MCV lines expressed both sLe(x) and sLe(a). Sialyl Le(x) was associated with glycoprotein(s) in M10-v, and sLe(a) occurred as a glycolipid moiety in M24. MCV recipients developed high titers for immunoglobulin (Ig)M but not IgG to both ligands. IgM titers to these ligands were low in normal subjects. In some of the preimmune sera of patients, the titers were threefold above normal. Six of 13 MCV recipients developed at least a twofold increase in anti-sLe titers above preimmune level after the second or third immunization. Adsorption studies suggested that both ligands were immunogenic.


CONCLUSIONS
The melanoma-associated sLe(x) and sLe(a) are immunogenic neoplasm-differentiation antigens and are therefore potential targets for passive and active specific immunotherapy in the treatment of melanoma.
Ravindranath
M H
MH
Roy E. Coats Research Laboratories of John Wayne Cancer Institute at Saint John's Hospital and Health Center, Santa Monica, California 90404, USA.
Amiri
A A
AA
Bauer
P M
PM
Kelley
M C
MC
Essner
R
R
Morton
D L
DL
D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000276:immunology* / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D001706:Biopsy; D018395:CA-19-9 Antigen; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000276:immunology; D004730:Endothelium, Vascular / Q000378:metabolism; D005732:Gangliosides / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009844:Oligosaccharides / Q000276:immunology* / Q000378:metabolism; D019087:Selectins / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D018395:CA-19-9 Antigen; D019496:Cancer Vaccines; D005732:Gangliosides; D008024:Ligands; D009844:Oligosaccharides; D019087:Selectins; D000080506:Sialyl Lewis X Antigen; C064564:sialyl Le(a) ganglioside