Vaccination with a DNA vaccine based on human PSCA and HSP70 adjuvant enhances the antigen‐specific CD8<sup>+</sup> T‐cell response and inhibits the PSCA<sup>+</sup> tumors growth in mice

Zhang, Xiaopeng; Yu, Changming; Zhao, Jian; Fu, Ling; Yi, Shaoqiong; Liu, Shilin; Takata, Yasuyuki; Chen, Wei

doi:10.1002/jgm.1067

Cited by 40 publications

(29 citation statements)

References 44 publications

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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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“…In the past few years, the function of HSP70 with immunoadjuvants has been identified, and large amounts of scientific literature have confirmed that vaccination with both HSP70-peptide complexes and HSP70-antigen fusion proteins reconstituted in vitro with genetic recombination can elicit antitumor immune responses. [20][21][22][23] Zhang et al 24 reported that HSP70 could increase the potency of DNA vaccine based on PSCA with strong cellular and humoral …”

Section: Discussionmentioning

confidence: 99%

“…However, compared with the results of Zhang et al, 25 the tumor cells established in our study grew faster in vivo. Both Zhang et al 24 and Zhang et al 25 suggested that immunization with pcDNA-PSCA alone hardly incited strong PSCA-specific immune responses and inhibited the growth of PSCA-expressing tumors, while we found that immunization with PSCA protein alone could incite effective immunologic response. In addition, human HSP70 could enhance the potency of the fusion protein vaccine based on PSCA in vivo, which enhanced PSCA-specific cellular and humoral immune responses and inhibited the growth of PSCA-expressing tumors of vaccinated mice.…”

mentioning

confidence: 83%

“…Moreover, coupling antigens to the aminoterminus of HSP70 could induce stronger immune responses than to the carboxyl-terminus. 24 Zhang et al 25 recently prepared the DNA/peptide combined vaccine based on PSCA, and the vaccination of mice with this complex induced a potent antitumor immunity to prostate carcinomas in a xenograft tumor model in nude mice. Karan et al 26 showed that adenovirus vaccine with PSCA and PSA coexpressing could induce strong PSCA-specific immune responses, and inhibit the growth of PSCA-expressing and PSA-expressing tumors.…”

mentioning

confidence: 99%

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Human Prostate Stem Cell Antigen and HSP70 Fusion Protein Vaccine Inhibits Prostate Stem Cell Antigen-Expressing Tumor Growth in Mice

Dong

Zhang

Ren

et al. 2013

Cancer Biotherapy and Radiopharmaceuticals

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Prostate stem cell antigen (PSCA) has been considered a potentially worthwhile target for prostate cancer therapy with its overexpression in both androgen-dependent and androgen-independent prostate cancers. However, PSCA is an autoantigen that can evoke immunological tolerance and hardly incite effective immunologic response. In this study, we sought to construct the fusion protein vaccines based on PSCA and heat shock protein 70 (HSP70) and to evaluate their immune responses and therapeutic efficacy. A series of recombinant proteins were prepared, and then, the male C57BL/6 mice were immunized subcutaneously by inoculation with RM-PSCA/Luc cells. The PSCA-specific cellular immune responses were monitored with ELISPOT and intracellular cytokines staining assay, and ELISA assay was used to detect humoral immune responses. The tumor growth was observed by in vivo bioluminescence imaging. The results showed that the mice vaccinated with PSCA-HSP could induce the PSCA-specific cellular and humoral immune responses. Tumor progression could be quantitatively monitored by in vivo bioluminescence imaging. Animal experiments showed that PSCA-HSP could inhibit the growth of PSCA-expressing tumors and prolong the survival time of vaccinated mice. This study supported and confirmed the potential of HSP70 as a chaperone for protein vaccines, and PSCA-HSP could be of potential value for prostate cancer treatment.

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“…The result depicted that mice vaccinated with PSCA-HSP plasmids triggered strongest PSCA-specific CD8 ? T cell immunological response (Zhang et al 2007). Consistent with same concept, recombinant adeno-associated virus (AAV) type 2 vectors are useful for antigen gene-loading of human DCs and for the rapid generation of cytotoxic T lymphocytes (CTL).…”

Section: Dna Vaccines: Well-equipped Swordsman For the Battlefieldmentioning

confidence: 99%

Prostate Cancer and Immunoproteome: Awakening and Reprogramming the Guardian Angels

Farooqı

Fayyaz

Qureshi

et al. 2012

Arch. Immunol. Ther. Exp.

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Prostate cancer is a life-threatening molecular disorder that is undruggable to date because of stumbling blocks in the standardization of therapy. An emerging framework of research is addressing how pathways that are derailed during tumorigenesis are linked to immunological responses, which are instrumental in immunosurveillance of cancer. However, interestingly, cancer cells circumvent such immunosurveillance through development of poorly immunogenic tumor cell variants (immunoselection) and through subversion of the immunological nanomachinery (immunosubversion). Detailed mechanistic insights of molecular specificities that regulate natural killer (NK) cell function suggest that it might be promising to design NK cell-based immunotherapeutic interventions against prostate cancer. Here, we elucidate evidence for NK cell targeting of prostate cancer proteome and address critical questions that, in our view, need thoughtfulness for the development of successful NK cell-based therapies. This review also disproves our contemporary understanding of the versatile regulators of DNA damage repair (ATM, ATR) that trigger cell surface expression of NKG2D ligands and consequent elimination of the tumor cells by NK cells and other lymphocytes that express NK cell receptors. Substantial fraction of information has been generated that guarantees productive future for this technology as more optimized constructs, better trial designs, and improved platforms are being brought from benchtop to bedside.

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Vaccination with a DNA vaccine based on human PSCA and HSP70 adjuvant enhances the antigen‐specific CD8⁺ T‐cell response and inhibits the PSCA⁺ tumors growth in mice

Abstract: These observations emphasize and extend the potential of the human HSP70 gene as adjuvant for DNA vaccines, and the vaccine based on PSCA and HSP70 is of potential value for treating prostate cancer.

Cited by 40 publications

References 44 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

Human Prostate Stem Cell Antigen and HSP70 Fusion Protein Vaccine Inhibits Prostate Stem Cell Antigen-Expressing Tumor Growth in Mice

Prostate Cancer and Immunoproteome: Awakening and Reprogramming the Guardian Angels

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Vaccination with a DNA vaccine based on human PSCA and HSP70 adjuvant enhances the antigen‐specific CD8+ T‐cell response and inhibits the PSCA+ tumors growth in mice

Abstract: These observations emphasize and extend the potential of the human HSP70 gene as adjuvant for DNA vaccines, and the vaccine based on PSCA and HSP70 is of potential value for treating prostate cancer.

Cited by 40 publications

References 44 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

Human Prostate Stem Cell Antigen and HSP70 Fusion Protein Vaccine Inhibits Prostate Stem Cell Antigen-Expressing Tumor Growth in Mice

Prostate Cancer and Immunoproteome: Awakening and Reprogramming the Guardian Angels

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Vaccination with a DNA vaccine based on human PSCA and HSP70 adjuvant enhances the antigen‐specific CD8⁺ T‐cell response and inhibits the PSCA⁺ tumors growth in mice