Generation of anti-tumor immunity using mammalian heat shock protein 70 DNA vaccines for cancer immunotherapy

Li, Ying; Subjeck, John R.; Yang, Gary; Repasky, Elizabeth A.; Wang, Xiangyang

doi:10.1016/j.vaccine.2006.04.028

Cited by 52 publications

(58 citation statements)

References 57 publications

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“…In several antigenic systems, depletion of CD4 T cells has no impact on the ability to prime CD8 T cells following hsp70 immunization (21)(22)(23), an observation that is remarkably similar to mice immunized with another HSP, gp96 (24). Because CD40-ligand is provided largely by CD4 T cells, these data would lend support to our conclusions in this study, a lack of a necessary interaction between hsp70 and CD40.…”

Section: Discussionsupporting

confidence: 80%

CD40-Independent Engagement of Mammalian hsp70 by Antigen-Presenting Cells

Binder

2009

The Journal of Immunology

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CD40 has been suggested previously to be a receptor for mammalian murine hsc73 (hsp70). We have examined, in vitro and in vivo, the role of CD40 in the interaction of murine dendritic cells and macrophages with hsp70, using several independent parameters including cell surface binding, translocation of NF-κB, stimulation of release of TNF-α, representation of hsp70-chaperoned peptides, and priming of CD8+ T cells. The various consequences of hsp70-APC interaction were compared between CD40+/+ and CD40−/− mice and were found to be identical in kinetics and magnitude. These data strongly indicate that all known effects of mammalian hsp70 on APCs are mediated in a CD40-independent manner. In light of the earlier demonstration that mycobacterial hsp70 binds murine CD40 and stimulates the APCs through it, our data indicate that CD40 can discriminate between self and mycobacterial hsp70 and is thus a receptor for patterns associated with microbial pathogens.

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Section: Discussionsupporting

confidence: 80%

CD40-Independent Engagement of Mammalian hsp70 by Antigen-Presenting Cells

Binder

2009

The Journal of Immunology

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“…Thus, the complexes are processed in a proteasome-dependent manner in the cytosol and are presented via MHC class I or MHC class II molecules, which then induces the activation of antigen-specific CD8 + or CD4 + T-cell responses, respectively (91)(92)(93). Because HSP-antigen complexes can induce the adaptive immune response, Hsp70 has been used as an adjuvant in vaccinations to enhance the immunogenicity of tumor antigens (94,95). Chaperokine, a term coined by Asea, describes the dual role of HSP as chaperones and cytokines.…”

Section: Cellular Responsementioning

confidence: 99%

Heat Shock Protein 70: Roles in Multiple Sclerosis

Mansilla

Montalbán

Espejo

2012

Mol Med

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Heat shock proteins (HSP) have long been considered intracellular chaperones that possess housekeeping and cytoprotective functions. Consequently, HSP overexpression was proposed as a potential therapy for neurodegenerative diseases characterized by the accumulation or aggregation of abnormal proteins. Recently, the discovery that cells release HSP with the capacity to trigger proinflammatory as well as immunoregulatory responses has focused attention on investigating the role of HSP in chronic inflammatory autoimmune diseases such as multiple sclerosis (MS). To date, the most relevant HSP is the inducible Hsp70, which exhibits both cytoprotectant and immunoregulatory functions. Several studies have presented contradictory evidence concerning the involvement of Hsp70 in MS or experimental autoimmune encephalomyelitis (EAE), the MS animal model. In this review, we dissect the functions of Hsp70 and discuss the controversial data concerning the role of Hsp70 in MS and EAE.

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“…Universally applicable novel HSP-mediated strategies have been devised because of limitations with isolation of HSPs from tumor as autologous vaccine (Castelli et al 2004;Gordon and Clark 2004). One of the strategies taken so far is DNA vaccination using HSP70 gene fused to or co-administered with a candidate antigen (Chen et al 2000;Geng et al 2006;Hsu et al 2001;Kim et al 2005;Lan et al 2007;Li et al 2006Li et al , 2007Liso et al 2005;Ma et al 2005;Pavlenko et al 2004;Wang et al 2004;Ye et al 2004;Zhang and Huang 2006;Zhang et al 2007). One study demonstrated that DNA vaccine containing HSP70 fused to C-terminal domain of Her2/neu could combat an aggressive Her2-expressing tumor (Kim et al 2005).…”

Section: Introductionmentioning

confidence: 99%

N-terminally fusion of Her2/neu to HSP70 decreases efficiency of Her2/neu DNA vaccine

Pakravan

Soudi

Hassan

2010

Cell Stress and Chaperones

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DNA vaccines consisted of tumor-associated antigen (TAA) are well suited for immunotherapy against tumor. The construct can contain TAA fused to an appropriate molecule (biologic adjuvant) to improve the efficacy of anti-tumor immune response. Heat shock protein 70 (HSP70) has been shown to be an excellent candidate, capable of cross-priming TAA by antigen presenting cells leading to a robust T-cell response. However, the relationship between strong T-cell responses and tumor rejection is not always mutually exclusive, for which TAA loss or activation of suppressive mechanisms may occur. HSP70 fused to downstream of Her2/neu as DNA vaccine has been shown to be efficient against Her2-expressing tumors. In this study, we examined if N-terminally fusion of Her2/neu to HSP70 could also improve efficiency of Her2/neu DNA vaccine. Therefore, mice with an established Her2/neu expressing tumor were immunized with DNA vaccine consisting of extracellular and trans-membrane domain (EC+TM) of rat Her2/neu alone or N-terminally fused to HSP70 and immune response was evaluated. Administration of rat Her2/neu led to partial control of tumor progression. Surprisingly, fusion of HSP70 to N-terminal of rat Her2/neu led to tumor progression. Our result proposes that fusion direction of biologic adjuvant is an important consideration when Her2/neu is used.

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Generation of anti-tumor immunity using mammalian heat shock protein 70 DNA vaccines for cancer immunotherapy

Cited by 52 publications

References 57 publications

CD40-Independent Engagement of Mammalian hsp70 by Antigen-Presenting Cells

CD40-Independent Engagement of Mammalian hsp70 by Antigen-Presenting Cells

Heat Shock Protein 70: Roles in Multiple Sclerosis

N-terminally fusion of Her2/neu to HSP70 decreases efficiency of Her2/neu DNA vaccine

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