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Natural killer (NK) cells are important effectors of innate immunity. In contrast to many studies of interleukin-2 (IL-2)-activated NK cells, the physiologic requirements for stimulating resting NK cells have only recently received attention. Given the emerging variety of dendritic cell (DC) types and their division of labor for stimulating immunity, we(More)
We studied the feasibility of using single-wall carbon nanotubes (SWNTs) as antigen carriers to improve immune responses to peptides that are weak immunogens, a characteristic typical of human tumor antigens. Binding and presentation of peptide antigens by the MHC molecules of antigen presenting cells (APCs) is essential to mounting an effective immune(More)
PURPOSE Wilms' tumor 1 protein (WT1), a transcription factor overexpressed in malignant mesothelioma, leukemias, and other solid tumors, is an ideal target for immunotherapy. WT1 class I peptide epitopes that were identified and shown to stimulate CD8(+) T cells are being tested as vaccine candidates in several clinical trials. The induction and maintenance(More)
A pilot study was undertaken to assess the safety, activity, and immunogenicity of a polyvalent Wilms tumor gene 1 (WT1) peptide vaccine in patients with acute myeloid leukemia in complete remission but with molecular evidence of WT1 transcript. Patients received 6 vaccinations with 4 WT1 peptides (200 microg each) plus immune adjuvants over 12 weeks.(More)
Intracellular tumor antigens presented on the cell surface in the context of human leukocyte antigen (HLA) molecules have been targeted by T cell-based therapies, but there has been little progress in developing small-molecule drugs or antibodies directed to these antigens. Here we describe a bispecific T-cell engager (BiTE) antibody derived from a T-cell(More)
Cyclin D1 is over-expressed in various human tumors and therefore can be a potential oncogenic target antigen. However, only a limited number of T cell epitopes has been characterized. We aimed at identifying human cyclin D1-derived peptides that include both CD4 and CD8 T cell epitopes and to test if such multi-epitope peptides could yield improved(More)
Wilms tumor protein (WT1) is a transcription factor selectively overexpressed in leukemias and cancers; clinical trials are underway that use altered WT1 peptide sequences as vaccines. Here we report a strategy to study peptide-MHC interactions by incorporating non-natural and photo-reactive amino acids into the sequence of WT1 peptides. Thirteen WT1(More)
Purpose: RMFPNAPYL (RMF), a Wilms' tumor gene 1 (WT1)–derived CD8 T-cell epitope presented by HLA-A Ã 02:01, is a validated target for T-cell–based immunotherapy. We previously reported ESK1, a high avidity (K d < 0.2 nmol/L), fully-human monoclonal antibody (mAb) specific for the WT1 RMF peptide/ HLA-A Ã 02:01 complex, which selectively bound and killed(More)
Approved therapeutic antineoplastic antibodies have targeted extracellular or cell-surface molecules. ESK1 is the first fully human T-cell receptor-like antibody targeting an intracellular tumor-associated antigen, Wilm's tumor 1 (WT1). In murine xenograft models, ESK1 exhibits a high specificity and exert robust antineoplastic effects against human cancers(More)