Interleukin-2-induced, melanoma-specific T cells recognize CAMEL, an unexpected translation product of LAGE-1.
Melanoma-specific cytotoxic T lymphocytes (CTLs) were induced by in vitro stimulation of peripheral blood mononuclear cells of a melanoma patient with autologous IL-2-producing melanoma 518/IL2.14 cells. CTL clone 1/29 recognized, in addition to autologous melanoma cell lines, a panel of HLA-A*0201-expressing allogeneic melanoma cell lines but was not reactive with normal melanocytes. Here, we report the full molecular characterization of the target structure for CTL 1/29, which was identified by cDNA expression cloning. The recognized antigen was named CAMEL (CTL-recognized antigen on melanoma). The CAMEL cDNA turned out to be derived from the LAGE-1 gene, a recently described tumor antigen that is strongly homologous to NY-ESO-1. CAMEL, however, is not encoded by the putative open reading frame (ORF) of LAGE-1 but by an alternative frame starting from the second ATG of the mRNA. The first 11 amino acids of the CAMEL protein, MLMAQEALAFL, constitute the epitope of CTL 1/29. This epitope is also encoded by a similar alternative ORF in NY-ESO-1. In summary, CTL induction with IL-2-transfected melanoma cells has revealed a new tumor antigen that may serve as a target for immunotherapy.
Department of Clinical Oncology, Leiden University Medical Center, The Netherlands.
C A
CA
Aarnoudse
P B
PB
van den Doel
B
B
Heemskerk
P I
PI
Schrier
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000235:genetics*; D001483:Base Sequence; D019556:COS Cells; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D018604:Epitope Mapping; D005815:Genetic Code; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis / Q000187:drug effects*; D012689:Sequence Homology, Nucleic Acid; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D007376:Interleukin-2