Antitumor immunity induced by DNA vaccine encoding alpha-fetoprotein/heat shock protein 70

Wang, Xiaoping; Liu, Guozhen; Ai-li, Song; Li, Haiyan; Lu, Yu

doi:10.3748/wjg.v10.i21.3197

Cited by 23 publications

(20 citation statements)

References 23 publications

(15 reference statements)

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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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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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“…How to enhance host's active immunity to AFP may be an interesting strategy for HCC therapy. Previous studies on AFP specific immunothereapy for HCC included AFP plasmid immunization, AFP-transduced dendritic cells (DCs) immunization and AFP plasmid prime-AFP adenovirus boost immunization [10][11][12][13][14]. AFP plasmid immunization produced detectable but low levels of AFP specific T cell responses and poorly reproducible protective immunity [4][5][6][7].…”

Section: Resultsmentioning

confidence: 99%

“…However, the need for costly cell culture procedures limited their wide availability for clinical use, and the unstable culture technique might yield tolerating vaccine [15]. AFP plasmid prime-AFP adenovirus boost immunization could engender significant AFP specific T-cell responses and protective immunity in mice [12,13]. But the miscellaneous procedures precluded their use.…”

Section: Resultsmentioning

confidence: 99%

Alpha-fetoprotein Epitope Peptide Promoted the Proliferation of Primary Hepatocellular Carcinoma Cells

Lin¹,

Wang²,

Xu³

et al. 2015

Proceedings of the 2015 International Conference on Materials Engineering and Information Technology Applications

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Abstract. Alpha-fetoprotein (AFP) is an oncofetal protein during hepatocellular carcinoma (HCC) development which could promote tumor growth and inhibit active immunity, and it may serve as a target for immunotherapy. To further confirm the immunogenicity of AFP, we constructed a AFP eitope peptide vaccine which contained the specific antigen epitope. Our results demonstrated that although AFP epitope peptide induced a distinct level of antibody, it still inhibited dendritic cells, CD8 + T cells, natural killer cells responses and promoted the growth of AFP-expressing tumors. Our study suggests that AFP epitope peptide promoted the proliferation of hepatocellular carcinoma by inhibiting the effects of immune cells,which may be a better basis for further study on HCC immunotherapy.

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“…3 Activation of an HCC-specific immune response can be accomplished by targeting tumor-associated self-antigens. In contrast to the immunotherapy using coimmunization with an AFP DNA vaccine and an immune response stimulator, such as, heat-shock protein70 20 and CTLA4, 21 the attenuated S. typhimurium oral DNA vaccines provide dual effects in one administration. The attenuated S. typhimurium not only serves as a DNA vaccine delivery vehicle but also an immune response stimulator.…”

Section: Discussionmentioning

confidence: 99%

An attenuated Salmonella oral DNA vaccine prevents the growth of hepatocellular carcinoma and colon cancer that express α-fetoprotein

et al. 2006

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Antitumor vaccination therapies using attenuated Salmonella typhimurium carrying plasmid DNA encoding tumor-associated antigens are currently under preclinical development. In the present study, we first established a useful method to facilitate in vivo monitoring of attenuated S. typhimurium uptake using a bioluminescent lux gene operon plasmid. Following transformation with the lux gene operon construct, mice were fed with various amounts of attenuated S. typhimurium-lux to monitor in vivo clearance over a period of 24 h. We found that the ingested attenuated S. typhimurium-lux cells were almost cleared out 9 h postfeeding, as judged by a significant decrease in bioluminescence. We further examined the therapeutic efficacy of vaccination using attenuated S. typhimurium carrying the mouse a-fetoprotein (AFP) gene against a cancer line CT26-murine a-feto protein (mAFP) that stably expresses AFP and mouse hepatocellular carcinoma (HCC) Hepa1-6. Attenuated S. typhimurium oral DNA vaccine was found to promote protective immunity against both CT26-mAFP and Hepa1-6 tumor cells growth. The oral DNA vaccine significantly increased the life span of tumor-challenged mice in both tumor models. Together, these results suggest that vaccination with the attenuated S. typhimurium oral DNA vaccine that carries the AFP gene could be a promising strategy to prevent HCC development.

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Antitumor immunity induced by DNA vaccine encoding alpha-fetoprotein/heat shock protein 70

Cited by 23 publications

References 23 publications

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

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

Alpha-fetoprotein Epitope Peptide Promoted the Proliferation of Primary Hepatocellular Carcinoma Cells

An attenuated Salmonella oral DNA vaccine prevents the growth of hepatocellular carcinoma and colon cancer that express α-fetoprotein

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