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*
Surgery Branch, Division of Clinical Sciences, National Cancer Institute, and
Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892
Twenty separate tumor infiltrating lymphocyte (TIL) bulk cultures
and a tumor cell line were originated simultaneously from a fine needle
aspiration biopsy of a metastasis in a patient with melanoma (F001)
previously immunized with the HLA-A*0201-associated gp100:209–217(210
M) peptide. None of the TIL recognized gp100. However, 12 recognized
autologous (F001-MEL) and allogeneic melanoma cells expressing the HLA
haplotype A*0201, B*0702, Cw*0702. Further characterization of F001-MEL
demonstrated loss of gp100/PMel17, severely decreased expression of
other melanoma differentiation Ags and retained expression of
tumor-specific Ags. Transfection of HLA class I alleles into
B*0702/Cw*0702-negative melanoma cell lines identified HLA-Cw*0702 as
the restriction element for F001-TIL. A cDNA library from F001-MEL was
used to transfect IFN-
-stimulated 293 human embryonal kidney
(293-HEK) cells expressing HLA-Cw*0702. A 100-gene pool was identified
that induced recognition of 293-HEK cells by F001-TIL. Subsequent
cloning of the pool identified a cDNA sequence homologous, except for
one amino acid (aa 187 D
A), to MAGE-12. Among 25 peptide sequences
from MAGE-12 with the HLA-Cw*0702 binding motif, MAGE-12:170–178
(VRIGHLYIL) induced IFN-
release by F001-TIL when pulsed on
F001-EBV-B cells at concentrations as low as 10 pg/ml. Peptide
sequences from MAGE-1, 2, 3, 4a, and 6 aligned to MAGE-12:170–178 were
not recognized by F001-TIL. In summary a TIL recognizing a MAGE protein
was developed from an HLA-A*0201 expressing tumor with strongly reduced
expression of melanoma differentiation Ags. Persisting tumor-specific
Ag expression maintained tumor immune competence suggesting that
tumor-specific Ags/melanoma differentiation Ags may complement each
other in the context of melanoma Ag-specific
vaccination.
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