| Efficient induction of a Her2-specific anti-tumor response by dendritic cells pulsed with a Hsp70L1-Her2(341-456) fusion protein. | |
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MedLine Citation:
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PMID: 21785448 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Heat shock proteins (HSPs) have been shown to interact with antigen-presenting cells (APCs), especially dendritic cells (DCs). HSPs act as potent adjuvants, inducing a Th1 response, as well as antigen-specific CD8(+) cytotoxic T lymphocytes (CTL) via cross-presentation. Our previous work has demonstrated that Hsp70-like protein 1 (Hsp70L1), a new member of the Hsp70 subfamily, can act as a powerful Th1 adjuvant in a DC-based vaccine. Here we report the efficient induction of tumor antigen-specific T cell immune response by DCs pulsed with recombinant fusion protein of Hsp70L1 and Her2(341-456), the latter of which is a fragment of Her2/neu (Her2) containing E75 (a HLA-A2 restricted CTL epitope). The fusion protein Hsp70L1-Her2(341-456) promotes the maturation of DCs and activates them to produce cytokines, such as IL-12 and TNF-α, and chemokines, such as MIP-1α, MIP-1β and RANTES. Taken together, these results indicate that the adjuvant activity of Hsp70L1 is maintained in the fusion protein. Her2-specific HLA-A2.1-restricted CD8(+) CTLs can be generated efficiently either from the Peripheral blood lymphocytes (PBL) of healthy donors or from the splenocytes of immunized HLA-A2.1/K(b) transgenic mice by in vitro stimulation or immunization with DCs pulsed with the Hsp70L1-Her2(341-456) fusion protein. This results in more potent target cell killing in an antigen-specific and HLA-A2.1-restricted manner. Adoptive transfer of splenocytes from transgenic mice immunized with Hsp70L1-Her2(341-456)-pulsed DCs can markedly inhibit tumor growth and prolong the survival of nude mice with Her2(+)/HLA-A2.1(+) human carcinomas. These results suggest that Hsp70L1-Her2(341-456)-pulsed DCs could be a new therapeutic vaccine for patients with Her2(+) cancer.Cellular & Molecular Immunology advance online publication, 25 July 2011; doi:10.1038/cmi.2011.21. |
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Authors:
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Qiang Fu; Yanfeng Wu; Fang Yan; Ning Wang; Wenying Wang; Xuetao Cao; Yajie Wang; Tao Wan |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-25 |
Journal Detail:
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Title: Cellular & molecular immunology Volume: - ISSN: 2042-0226 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101242872 Medline TA: Cell Mol Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Oncology, Changhai Hospital of Shanghai, Shanghai 200433, China. |
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