Antimelanoma CTL recognizes peptides derived from an ORF transcribed from the antisense strand of the 3' untranslated region of TRIT1.
Noncoding regions of the genome play an important role in tumorigenesis of cancer. Using expression cloning, we have identified a cytotoxic T lymphocyte (CTL)-defined antigen that recognizes a protein sequence derived from an open reading frame transcribed from the reverse strand in the 3' untranslated region of tRNA isopentenyltransferase 1 (TRIT1). A peptide derived from this open reading frame (ORF) sequence and predicted to bind to HLA-B57, sensitized HLA-B57(+) tumor cells to lysis by CTL793. The peptide also induced a CTL response in peripheral blood mononuclear cells (PBMC) of patient 793 and in two other melanoma patients. The CTL lysed peptide-pulsed HLA-B57(+) target cells and melanoma cells with endogenous antigen expression. The recognition of this antigen is not limited to HLA-B57-restricted CTLs. An HLA-A2 peptide derived from the ORF was able to induce CTLs in PBMC of 2 HLA-A2(+) patients. This study describes for the first time a CTL-defined melanoma antigen that is derived from an ORF on the reverse strand of the putative tumor suppressor gene TRIT1. This antigen has potential use as a vaccine or its ability to induce CTLs in vitro could be used as a predictive biomarker.
The Wistar Institute , Philadelphia, Pennsylvania, USA.
Rolf K
RK
Swoboda
The Wistar Institute , Philadelphia, Pennsylvania, USA.
Rajasekharan
R
Somasundaram
The Wistar Institute , Philadelphia, Pennsylvania, USA.
Laura
L
Caputo-Gross
Department of Transfusion Medicine Clinical Center, National Institutes of Health , Bethesda, Maryland, USA.
Francesco M
FM
Marincola
Surgery Branch, National Cancer Institute, National Institutes of Health , Bethesda, Maryland, USA.
Paul
P
Robbins
The Wistar Institute , Philadelphia, Pennsylvania, USA.
Meenhard
M
Herlyn
The Wistar Institute , Philadelphia, Pennsylvania, USA.
Dorothee
D
Herlyn