Cancer/testis antigens can be immunological targets in clonogenic CD133+ melanoma cells.
"Cancer stem cells" that resist conventional treatments may be a cause of therapeutic failure in melanoma. We report a subpopulation of clonogenic melanoma cells that are characterized by high prominin-1/CD133 expression in melanoma and melanoma cell lines. These cells have enhanced clonogenicity and self-renewal in vitro, and serve as a limited in vitro model for melanoma stem cells. In some cases clonogenic CD133(+) melanoma cells show increased expression of some cancer/testis (CT) antigens. The expression of NY-ESO-1 in an HLA-A2 expressing cell line allowed CD133(+) clonogenic melanoma cells to be targeted for killing in vitro by NY-ESO-1-specific CD8(+) T-lymphocytes. Our in vitro findings raise the hypothesis that if melanoma stem cells express CT antigens in vivo that immune targeting of these antigens may be a viable clinical strategy for the adjuvant treatment of melanoma.
Gedye
Craig
C
Ludwig Institute for Cancer Research, Austin Hospital, Studley Road, Heidelberg, VIC, 3084, Australia. craig.gedye@ludwig.edu.au
Quirk
Juliet
J
Browning
Judy
J
Svobodová
Suzanne
S
John
Thomas
T
Sluka
Pavel
P
Dunbar
P Rod
PR
Corbeil
Denis
D
Cebon
Jonathan
J
Davis
Ian D
ID
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003114:Colony-Forming Units Assay; D003602:Cytotoxicity, Immunologic; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000378:metabolism*; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000556:secondary / Q000628:therapy; D008565:Membrane Proteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000071916:AC133 Antigen; D015703:Antigens, CD; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D006023:Glycoproteins; D015789:HLA-A2 Antigen; D008565:Membrane Proteins; C000606023:PROM1 protein, human; D010446:Peptide Fragments; D010455:Peptides; D012333:RNA, Messenger