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* Clinical Cooperation Group Hyperthermie,
Institute of Molecular Immunology, GSF National Research Center for Environment and Health, and
Medizinische Klinik III, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany;
Institute of Pathology, GSF National Research Center for Environment and Health, Neuherberg, Germany; and
¶ Department of Radiation Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115
Our study demonstrates that tumor-derived heat shock protein
(HSP)70 chaperones a tyrosinase peptide and mediates its transfer to
human immature dendritic cells (DCs) by receptor-dependent uptake.
Human tumor-derived HSP70 peptide complexes (HSP70-PC) thus have the
immunogenic potential to instruct DCs to cross-present endogenously
expressed, nonmutated, and tumor antigenic peptides that are shared
among tumors of the melanocytic lineage for T cell recognition. T cell
stimulation by HSP70-instructed DCs is dependent on the Ag bound to
HSP70 in that only DCs incubated with HSP70-PC purified from
tyrosinase-positive (HSP70-PC/tyr+) but not from
tyrosinase-negative (HSP70-PC/tyr-) melanoma cells
resulted in the specific activation of the HLA-A*0201-restricted
tyrosinase peptide-specific cytotoxic T cell clone. HSP70-PC-mediated T
cell stimulation is very efficient, delivering the tyrosinase peptide
at concentrations as low as 30 ng/ml of HSP70-PC for T cell
recognition. Receptor-dependent binding of HSP70-PC and active cell
metabolism are prerequisites for MHC class I-restricted
cross-presentation and T cell stimulation. T cell stimulation does not
require external DC maturation signals (e.g., exogenously added
TNF-
), suggesting that signaling DC maturation is an intrinsic
property of the HSP70-PC itself and related to receptor-mediated
binding. The cross-presentation of a shared human tumor Ag together
with the exquisite efficacy are important new aspects for HSP70-based
immunotherapy in clinical anti-cancer vaccination strategies, and
suggest a potential extension of HSP70-based vaccination protocols from
a patient-individual treatment modality to its use in an allogeneic
setting.
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|
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|
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|
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