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Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892
Dramatic clinical responses were observed in patient 888 following
the adoptive transfer of autologous tumor-infiltrating lymphocytes
(TIL). Previously, extensive analysis of the specificity of class
I-restricted T cells from patient 888 TIL has revealed that these T
cells recognize a mutated, as well as several nonmutated tumor Ags.
Additional studies that were conducted on TIL from patient 888
indicated that they contained CD4-positive T cells that recognized the
autologous tumor that had been induced to express HLA class II
molecules. Tumor-reactive CD4-positive T cell clones were isolated from
TIL and tested for their ability to react with Ags that are recognized
by HLA class I-restricted, melanoma-reactive T cells. Using this
approach, T cell clones were identified that recognized an epitope
expressed in both the tyrosinase-related protein 1 and
tyrosinase-related protein 2 Ags in the context of the HLA-DR
1*1502
class II gene product. Additional clones were found to recognize an
epitope of gp100 in the context of the same HLA-DR restriction element.
These observations provide an impetus to develop strategies directed
toward generating HLA class II-restricted tumor-reactive T
cells.
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