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*
Department of Tumor Progression and Immune Defense, German Cancer Research Center, Heidelberg, Germany;
Department of Genomics and Information Sciences, Hoffmann-La Roche, Nutley, NY 07110;
Institute of Immunology, University of Heidelberg, Heidelberg, Germany; and
§
Department of Applied Genetics, University of Karlsruhe, Karlsruhe, Germany
The melanoma-associated Ag glycoprotein 100 was analyzed by the T
cell epitope prediction software TEPITOPE. Seven HLA-DR promiscuous
peptides predicted with a stringent threshold were used to load
dendritic cells (DC), and induction of a proliferative response was
monitored. PBMC of all nine donors including two patients with
malignant melanoma responded to at least one of the peptides. The
proliferative response was defined as a Th response by the selective
expansion of CD4+ cells, up-regulation of CD25 and CD40L,
and IL-2 and IFN-
expression. Peptide-loaded DC also initiated a T
helper response in vivo (i.e., tumor growth in the SCID mouse was
significantly retarded by the transfer of PBMC together with
peptide-loaded DC). Because the use of the TEPITOPE program allows for
a prediction of T cell epitopes; because the predicted peptides can be
rapidly confirmed by inducing a Th response in the individual patient;
and because application of peptide-loaded DC suffices for the in vivo
activation of helper cells, vaccination with MHC class II-binding
peptides of tumor-associated Ags becomes a feasible and likely powerful
tool in the immunotherapy of cancer.
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