I. Saeterdal et al., GENERATION AND CHARACTERIZATION OF GP100 PEPTIDE-SPECIFIC NK-T CELL CLONES, International journal of cancer, 75(5), 1998, pp. 794-803
MHC-restricted cytotoxic T lymphocytes (CTLs) specific for antigens ex
pressed by malignant cells are important components of immune response
s against human cancer. Peripheral blood monocytes of HLA-A2(+) health
y donors were used to induce dendritic cells (DCs) by granulocyte-macr
ophage colony-stimulating factor and interleukin-4 and loaded with a g
p100 peptide (YLEPGPVTA). By applying these peptide-loaded DCs, a CTL
line that displayed high cytotoxic reactivity with peptide-loaded targ
et cells was generated. A total of II gp100 peptide-specific CTL clone
s were generated from this cell line. Several of these CTL clones were
studied in detail. Of particular interest was clone CTL-45, which, co
ntrary to the parental cell line, displayed strong NK activity and, by
flow-cytometric analysis, revealed a CD3(+), TCR BV 17, CD8(+) and CD
56(+) phenotype. This clone was strictly peptide-specific and effectiv
ely killed a panel of melanoma cells expressing HLA-A2 and gp100. Tumo
r-specific T cells with this kind of dual function are potentially of
great clinical importance as they have a backup mechanism that may go
into action when tumor cells escape specific killing by losing their H
LA-class 1 molecules. (C) 1998 Wiley-Liss, Inc.