Generation of survivin-specific CD8+ T effector cells by dendritic cells pulsed with protein or selected peptides

The identification of tumor-associated antigens recognized by CD8(+) cytoto xic T cells paved the way to new concepts in adjuvant anticancer therapy. H owever, the number of tumor-associated proteins found to be expressed in th e majority of human cancers Is still rather limited. Recently, the newly id entified apoptosis inhibitor protein survivin has been recognized as a wide ly occurring tumor-associated protein. In the present study, we demonstrate that survivin is capable of inducing specific CD8(+) effector T cells in v itro. T cells from healthy donors were subjected to several cycles of stimu lation by autologous dendritic cells (DCs) pulsed with soluble recombinant survivin protein, Activation of CD8(+) cytotoxic T cells by survivin-derive d peptides cross-presented by DCs was demonstrated by lysis of autologous s urvivin-expressing B cell transfectants, Using a peptide-moth scoring syste m, two survivin peptides (ELTLGE-FLKL and TLPPAWQPFL) were predicted and pr oved to hind to the HLA-A*0201 molecule. Both peptides were shown to induce CD8(+) effector T cells when presented on DCs; one peptide could be verifi ed to result from natural intracellular processing of survivin. These findi ngs recommend survivin as a new and widely applicable target for protein- a nd peptide-based immunotherapy of tumors.