Enhanced Immunogenicity of Heat Shock Protein 70 Peptide Complexes from Dendritic Cell-Tumor Fusion Cells
| Autor: | Chunlei Liu, Ajit Bharti, Baizheng Song, Vasso Apostolopoulos, Stuart K. Calderwood, Yutaka Enomoto, Jianlin Gong, Pei-Xiang Xing, Ad Abdul Khaleque |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
T-Lymphocytes
T cell Immunology Biology Cancer Vaccines Cell Fusion Mice Interleukin 21 Immune system Neoplasms medicine Animals Immunology and Allergy Cytotoxic T cell HSP70 Heat-Shock Proteins IL-2 receptor Antigen-presenting cell Mice Knockout Mucin-1 Toll-Like Receptors Dendritic Cells Dendritic cell Molecular biology Peptide Fragments Cell biology Immunity Active medicine.anatomical_structure Multiprotein Complexes Myeloid Differentiation Factor 88 Interleukin 12 Immunization Peptides |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | We have developed a molecular chaperone-based tumor vaccine that reverses the immune tolerance of cancer cells. Heat shock protein (HSP) 70 extracted from fusions of dendritic (DC) and tumor cells (HSP70.PC-F) possess superior properties such as stimulation of DC maturation and T cell proliferation over its counterpart from tumor cells. More importantly, immunization of mice with HSP70.PC-F resulted in a T cell-mediated immune response including significant increase of CD8 T cells and induction of the effector and memory T cells that was able to break T cell unresponsiveness to a nonmutated tumor Ag and provide protection of mice against challenge with tumor cells. By contrast, the immune response to vaccination with HSP70-PC derived from tumor cells is muted against such nonmutated tumor Ag. HSP70.PC-F complexes differed from those derived from tumor cells in a number of key manners, most notably, enhanced association with immunologic peptides. In addition, the molecular chaperone HSP90 was found to be associated with HSP70.PC-F as indicated by coimmunoprecipitation, suggesting ability to carry an increased repertoire of antigenic peptides by the two chaperones. Significantly, activation of DC by HSP70.PC-F was dependent on the presence of an intact MyD88 gene, suggesting a role for TLR signaling in DC activation and T cell stimulation. These experiments indicate that HSP70-peptide complexes (PC) derived from DC-tumor fusion cells have increased their immunogenicity and therefore constitute an improved formulation of chaperone protein-based tumor vaccine. |
| Databáze: | OpenAIRE |
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