The Experts below are selected from a list of 177 Experts worldwide ranked by ideXlab platform
Wenfang Cheng - One of the best experts on this subject based on the ideXlab platform.
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naked RNA Vaccine controls tumors with down regulated mhc class i expression through nk cells and perforin dependent pathways
European Journal of Immunology, 2004Co-Authors: Wenfang Cheng, Chienfu Hung, Liangmei He, Tzyy Choou Wu, Yi Ning Su, Ming Cheng Chang, Chian Chen, Chang Yao HsiehAbstract:One of the major issues facing cancer immunotherapy is that many human cancers down-regulate expression of MHC class I molecules. The understanding of the mechanisms of antitumor effects against tumors with down-regulated MHC class I will facilitate rational design of Vaccines and immunotherapeutic strategies to control such tumors. A naked Sindbis RNA replicon vector (SINrep5) encoding the herpes simplex virus type 1 protein VP22 linked to E7 (SINrep5-VP22/E7) generated significant antitumor effects against TC-1 and TC-1 P3(A15), tumors with down-regulated MHC class I expression. Naked SINrep5 RNA without the insert or an E7 Vaccine also produced antitumor effects against TC-1 P3(A15) but not TC-1. Mice vaccinated with any of these naked RNA Vaccines generated higher percentages of NK cells. In vivo Ab depletion experiments revealed that NK cells were important for the antitumor effects of naked RNA Vaccines against TC-1 P3(A15) and that the antitumor effects were perforin-dependent. Poly I:C also increased the percentage of NK cells and generated antitumor effects against the tumors with down-regulated MHC class I. Thus, the SINrep5-VP22/E7 naked RNA Vaccinecontrols MHC class I-positive and MHC class I-down-regulated tumor cells via different mechanisms, and NK cells play an important role in the antitumor effects generated by naked RNA replicon Vaccines.
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Naked RNA Vaccine controls tumors with down‐regulated MHC class I expression through NK cells and perforin‐dependent pathways
European Journal of Immunology, 2004Co-Authors: Wenfang Cheng, Chienfu Hung, Liangmei He, Tzyy Choou Wu, Yi Ning Su, Ming Cheng Chang, Chian Chen, Chang Yao HsiehAbstract:One of the major issues facing cancer immunotherapy is that many human cancers down-regulate expression of MHC class I molecules. The understanding of the mechanisms of antitumor effects against tumors with down-regulated MHC class I will facilitate rational design of Vaccines and immunotherapeutic strategies to control such tumors. A naked Sindbis RNA replicon vector (SINrep5) encoding the herpes simplex virus type 1 protein VP22 linked to E7 (SINrep5-VP22/E7) generated significant antitumor effects against TC-1 and TC-1 P3(A15), tumors with down-regulated MHC class I expression. Naked SINrep5 RNA without the insert or an E7 Vaccine also produced antitumor effects against TC-1 P3(A15) but not TC-1. Mice vaccinated with any of these naked RNA Vaccines generated higher percentages of NK cells. In vivo Ab depletion experiments revealed that NK cells were important for the antitumor effects of naked RNA Vaccines against TC-1 P3(A15) and that the antitumor effects were perforin-dependent. Poly I:C also increased the percentage of NK cells and generated antitumor effects against the tumors with down-regulated MHC class I. Thus, the SINrep5-VP22/E7 naked RNA Vaccinecontrols MHC class I-positive and MHC class I-down-regulated tumor cells via different mechanisms, and NK cells play an important role in the antitumor effects generated by naked RNA replicon Vaccines.
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enhancement of sindbis virus self replicating RNA Vaccine potency by linkage of mycobacterium tuberculosis heat shock protein 70 gene to an antigen gene
Journal of Immunology, 2001Co-Authors: Wenfang Cheng, Chienfu Hung, Cheeyin Chai, Morris Ling, Liangmai He, Charles M Rice, Tzyy Choou WuAbstract:Recently, self-replicating RNA Vaccines (RNA replicons) have emerged as an effective strategy for nucleic acid Vaccine development. Unlike naked DNA Vaccines, RNA replicons eventually cause lysis of transfected cells and therefore do not raise the concern of integration into the host genome. We evaluated the effect of linking human papillomavirus type 16 E7 as a model Ag to Mycobacterium tuberculosis heat shock protein 70 (HSP70) on the potency of Ag-specific immunity generated by a Sindbis virus self-replicating RNA vector, SINrep5. Our results indicated that this RNA replicon Vaccine containing an E7/HSP70 fusion gene generated significantly higher E7-specific T cell-mediated immune responses in vaccinated mice than did Vaccines containing the wild-type E7 gene. Furthermore, our in vitro studies demonstrated that E7 Ag from E7/HSP70 RNA replicon-transfected cells can be processed by bone marrow-derived dendritic cells and presented more efficiently through the MHC class I pathway than can wild-type E7 RNA replicon-transfected cells. More importantly, the fusion of HSP70 to E7 converted a less effective Vaccine into one with significant potency against E7-expressing tumors. This antitumor effect was dependent on NK cells and CD8 + T cells. These results indicated that fusion of HSP70 to an Ag gene may greatly enhance the potency of self-replicating RNA Vaccines.
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enhancement of sindbis virus self replicating RNA Vaccine potency by linkage of herpes simplex virus type 1 vp22 protein to antigen
Journal of Virology, 2001Co-Authors: Wenfang Cheng, Chienfu Hung, Cheeyin Chai, Morris Ling, Liangmai He, Tzyy Choou WuAbstract:Recently, self-replicating and self-limiting RNA Vaccines (RNA replicons) have emerged as an important form of nucleic acid Vaccines. Self-replicating RNA eventually causes lysis of transfected cells and does not raise the concern associated with naked DNA Vaccines of integration into the host genome. This is particularly important for development of Vaccines targeting proteins that are potentially oncogenic. However, the potency of RNA replicons is significantly limited by their lack of intrinsic ability to spread in vivo. The herpes simplex virus type 1 protein VP22 has demonstrated the remarkable property of intercellular transport and provides the opportunity to enhance RNA replicon Vaccine potency. We therefore created a novel fusion of VP22 with a model tumor antigen, human papillomavirus type 16 E7, in a Sindbis virus RNA replicon vector. The linkage of VP22 with E7 resulted in a significant enhancement of E7-specific CD8 + T-cell activities in vaccinated mice and converted a less effective RNA replicon Vaccine into one with significant potency against E7-expressing tumors. These results indicate that fusion of VP22 to an antigen gene may greatly enhance the potency of RNA replicon Vaccines.
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enhancement of sindbis virus self replicating RNA Vaccine potency by targeting antigen to endosomal lysosomal compartments
Human Gene Therapy, 2001Co-Authors: Wenfang Cheng, Chienfu Hung, Cheeyin Chai, Liangmei He, Morris Ling, Leigh A Slater, Richard B S Roden, Tzyy Choou WuAbstract:Self-replicating RNA Vaccines (RNA replicons) have emerged as an attractive approach for tumor immunotherapy. RNA replicons do not integrate into host chromosomes, eliminating the concern for oncogenicity associated with a DNA Vaccine. In this study, we used human papillomavirus type 16 (HPV-16) E7 as a model antigen and evaluated E7-specific immunity generated by a Sindbis virus self-replicating RNA vector, SIN-rep5. Three different constructs were created to target E7 antigen to different cellular localizations: (1) E7, a cytosolic/nuclear protein; (2) Sig/E7, a secretory protein; (3) Sig/E7/LAMP-1, in which we linked the transmembrane and cytoplasmic regions of the lysosome-associated membrane protein 1 (LAMP-1) to E7 protein to target E7 to the endosomal/lysosomal compartment. We found that the RNA replicon Vaccine containing the Sig/E7/LAMP-1 fusion gene generated the highest E7-specific T cell-mediated immune responses and antitumor effects relative to RNA Vaccines containing either wild-type E7 or ...
Tzyy Choou Wu - One of the best experts on this subject based on the ideXlab platform.
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naked RNA Vaccine controls tumors with down regulated mhc class i expression through nk cells and perforin dependent pathways
European Journal of Immunology, 2004Co-Authors: Wenfang Cheng, Chienfu Hung, Liangmei He, Tzyy Choou Wu, Yi Ning Su, Ming Cheng Chang, Chian Chen, Chang Yao HsiehAbstract:One of the major issues facing cancer immunotherapy is that many human cancers down-regulate expression of MHC class I molecules. The understanding of the mechanisms of antitumor effects against tumors with down-regulated MHC class I will facilitate rational design of Vaccines and immunotherapeutic strategies to control such tumors. A naked Sindbis RNA replicon vector (SINrep5) encoding the herpes simplex virus type 1 protein VP22 linked to E7 (SINrep5-VP22/E7) generated significant antitumor effects against TC-1 and TC-1 P3(A15), tumors with down-regulated MHC class I expression. Naked SINrep5 RNA without the insert or an E7 Vaccine also produced antitumor effects against TC-1 P3(A15) but not TC-1. Mice vaccinated with any of these naked RNA Vaccines generated higher percentages of NK cells. In vivo Ab depletion experiments revealed that NK cells were important for the antitumor effects of naked RNA Vaccines against TC-1 P3(A15) and that the antitumor effects were perforin-dependent. Poly I:C also increased the percentage of NK cells and generated antitumor effects against the tumors with down-regulated MHC class I. Thus, the SINrep5-VP22/E7 naked RNA Vaccinecontrols MHC class I-positive and MHC class I-down-regulated tumor cells via different mechanisms, and NK cells play an important role in the antitumor effects generated by naked RNA replicon Vaccines.
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Naked RNA Vaccine controls tumors with down‐regulated MHC class I expression through NK cells and perforin‐dependent pathways
European Journal of Immunology, 2004Co-Authors: Wenfang Cheng, Chienfu Hung, Liangmei He, Tzyy Choou Wu, Yi Ning Su, Ming Cheng Chang, Chian Chen, Chang Yao HsiehAbstract:One of the major issues facing cancer immunotherapy is that many human cancers down-regulate expression of MHC class I molecules. The understanding of the mechanisms of antitumor effects against tumors with down-regulated MHC class I will facilitate rational design of Vaccines and immunotherapeutic strategies to control such tumors. A naked Sindbis RNA replicon vector (SINrep5) encoding the herpes simplex virus type 1 protein VP22 linked to E7 (SINrep5-VP22/E7) generated significant antitumor effects against TC-1 and TC-1 P3(A15), tumors with down-regulated MHC class I expression. Naked SINrep5 RNA without the insert or an E7 Vaccine also produced antitumor effects against TC-1 P3(A15) but not TC-1. Mice vaccinated with any of these naked RNA Vaccines generated higher percentages of NK cells. In vivo Ab depletion experiments revealed that NK cells were important for the antitumor effects of naked RNA Vaccines against TC-1 P3(A15) and that the antitumor effects were perforin-dependent. Poly I:C also increased the percentage of NK cells and generated antitumor effects against the tumors with down-regulated MHC class I. Thus, the SINrep5-VP22/E7 naked RNA Vaccinecontrols MHC class I-positive and MHC class I-down-regulated tumor cells via different mechanisms, and NK cells play an important role in the antitumor effects generated by naked RNA replicon Vaccines.
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enhancement of sindbis virus self replicating RNA Vaccine potency by linkage of mycobacterium tuberculosis heat shock protein 70 gene to an antigen gene
Journal of Immunology, 2001Co-Authors: Wenfang Cheng, Chienfu Hung, Cheeyin Chai, Morris Ling, Liangmai He, Charles M Rice, Tzyy Choou WuAbstract:Recently, self-replicating RNA Vaccines (RNA replicons) have emerged as an effective strategy for nucleic acid Vaccine development. Unlike naked DNA Vaccines, RNA replicons eventually cause lysis of transfected cells and therefore do not raise the concern of integration into the host genome. We evaluated the effect of linking human papillomavirus type 16 E7 as a model Ag to Mycobacterium tuberculosis heat shock protein 70 (HSP70) on the potency of Ag-specific immunity generated by a Sindbis virus self-replicating RNA vector, SINrep5. Our results indicated that this RNA replicon Vaccine containing an E7/HSP70 fusion gene generated significantly higher E7-specific T cell-mediated immune responses in vaccinated mice than did Vaccines containing the wild-type E7 gene. Furthermore, our in vitro studies demonstrated that E7 Ag from E7/HSP70 RNA replicon-transfected cells can be processed by bone marrow-derived dendritic cells and presented more efficiently through the MHC class I pathway than can wild-type E7 RNA replicon-transfected cells. More importantly, the fusion of HSP70 to E7 converted a less effective Vaccine into one with significant potency against E7-expressing tumors. This antitumor effect was dependent on NK cells and CD8 + T cells. These results indicated that fusion of HSP70 to an Ag gene may greatly enhance the potency of self-replicating RNA Vaccines.
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enhancement of sindbis virus self replicating RNA Vaccine potency by linkage of herpes simplex virus type 1 vp22 protein to antigen
Journal of Virology, 2001Co-Authors: Wenfang Cheng, Chienfu Hung, Cheeyin Chai, Morris Ling, Liangmai He, Tzyy Choou WuAbstract:Recently, self-replicating and self-limiting RNA Vaccines (RNA replicons) have emerged as an important form of nucleic acid Vaccines. Self-replicating RNA eventually causes lysis of transfected cells and does not raise the concern associated with naked DNA Vaccines of integration into the host genome. This is particularly important for development of Vaccines targeting proteins that are potentially oncogenic. However, the potency of RNA replicons is significantly limited by their lack of intrinsic ability to spread in vivo. The herpes simplex virus type 1 protein VP22 has demonstrated the remarkable property of intercellular transport and provides the opportunity to enhance RNA replicon Vaccine potency. We therefore created a novel fusion of VP22 with a model tumor antigen, human papillomavirus type 16 E7, in a Sindbis virus RNA replicon vector. The linkage of VP22 with E7 resulted in a significant enhancement of E7-specific CD8 + T-cell activities in vaccinated mice and converted a less effective RNA replicon Vaccine into one with significant potency against E7-expressing tumors. These results indicate that fusion of VP22 to an antigen gene may greatly enhance the potency of RNA replicon Vaccines.
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enhancement of sindbis virus self replicating RNA Vaccine potency by targeting antigen to endosomal lysosomal compartments
Human Gene Therapy, 2001Co-Authors: Wenfang Cheng, Chienfu Hung, Cheeyin Chai, Liangmei He, Morris Ling, Leigh A Slater, Richard B S Roden, Tzyy Choou WuAbstract:Self-replicating RNA Vaccines (RNA replicons) have emerged as an attractive approach for tumor immunotherapy. RNA replicons do not integrate into host chromosomes, eliminating the concern for oncogenicity associated with a DNA Vaccine. In this study, we used human papillomavirus type 16 (HPV-16) E7 as a model antigen and evaluated E7-specific immunity generated by a Sindbis virus self-replicating RNA vector, SIN-rep5. Three different constructs were created to target E7 antigen to different cellular localizations: (1) E7, a cytosolic/nuclear protein; (2) Sig/E7, a secretory protein; (3) Sig/E7/LAMP-1, in which we linked the transmembrane and cytoplasmic regions of the lysosome-associated membrane protein 1 (LAMP-1) to E7 protein to target E7 to the endosomal/lysosomal compartment. We found that the RNA replicon Vaccine containing the Sig/E7/LAMP-1 fusion gene generated the highest E7-specific T cell-mediated immune responses and antitumor effects relative to RNA Vaccines containing either wild-type E7 or ...
Chienfu Hung - One of the best experts on this subject based on the ideXlab platform.
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naked RNA Vaccine controls tumors with down regulated mhc class i expression through nk cells and perforin dependent pathways
European Journal of Immunology, 2004Co-Authors: Wenfang Cheng, Chienfu Hung, Liangmei He, Tzyy Choou Wu, Yi Ning Su, Ming Cheng Chang, Chian Chen, Chang Yao HsiehAbstract:One of the major issues facing cancer immunotherapy is that many human cancers down-regulate expression of MHC class I molecules. The understanding of the mechanisms of antitumor effects against tumors with down-regulated MHC class I will facilitate rational design of Vaccines and immunotherapeutic strategies to control such tumors. A naked Sindbis RNA replicon vector (SINrep5) encoding the herpes simplex virus type 1 protein VP22 linked to E7 (SINrep5-VP22/E7) generated significant antitumor effects against TC-1 and TC-1 P3(A15), tumors with down-regulated MHC class I expression. Naked SINrep5 RNA without the insert or an E7 Vaccine also produced antitumor effects against TC-1 P3(A15) but not TC-1. Mice vaccinated with any of these naked RNA Vaccines generated higher percentages of NK cells. In vivo Ab depletion experiments revealed that NK cells were important for the antitumor effects of naked RNA Vaccines against TC-1 P3(A15) and that the antitumor effects were perforin-dependent. Poly I:C also increased the percentage of NK cells and generated antitumor effects against the tumors with down-regulated MHC class I. Thus, the SINrep5-VP22/E7 naked RNA Vaccinecontrols MHC class I-positive and MHC class I-down-regulated tumor cells via different mechanisms, and NK cells play an important role in the antitumor effects generated by naked RNA replicon Vaccines.
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Naked RNA Vaccine controls tumors with down‐regulated MHC class I expression through NK cells and perforin‐dependent pathways
European Journal of Immunology, 2004Co-Authors: Wenfang Cheng, Chienfu Hung, Liangmei He, Tzyy Choou Wu, Yi Ning Su, Ming Cheng Chang, Chian Chen, Chang Yao HsiehAbstract:One of the major issues facing cancer immunotherapy is that many human cancers down-regulate expression of MHC class I molecules. The understanding of the mechanisms of antitumor effects against tumors with down-regulated MHC class I will facilitate rational design of Vaccines and immunotherapeutic strategies to control such tumors. A naked Sindbis RNA replicon vector (SINrep5) encoding the herpes simplex virus type 1 protein VP22 linked to E7 (SINrep5-VP22/E7) generated significant antitumor effects against TC-1 and TC-1 P3(A15), tumors with down-regulated MHC class I expression. Naked SINrep5 RNA without the insert or an E7 Vaccine also produced antitumor effects against TC-1 P3(A15) but not TC-1. Mice vaccinated with any of these naked RNA Vaccines generated higher percentages of NK cells. In vivo Ab depletion experiments revealed that NK cells were important for the antitumor effects of naked RNA Vaccines against TC-1 P3(A15) and that the antitumor effects were perforin-dependent. Poly I:C also increased the percentage of NK cells and generated antitumor effects against the tumors with down-regulated MHC class I. Thus, the SINrep5-VP22/E7 naked RNA Vaccinecontrols MHC class I-positive and MHC class I-down-regulated tumor cells via different mechanisms, and NK cells play an important role in the antitumor effects generated by naked RNA replicon Vaccines.
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enhancement of sindbis virus self replicating RNA Vaccine potency by linkage of mycobacterium tuberculosis heat shock protein 70 gene to an antigen gene
Journal of Immunology, 2001Co-Authors: Wenfang Cheng, Chienfu Hung, Cheeyin Chai, Morris Ling, Liangmai He, Charles M Rice, Tzyy Choou WuAbstract:Recently, self-replicating RNA Vaccines (RNA replicons) have emerged as an effective strategy for nucleic acid Vaccine development. Unlike naked DNA Vaccines, RNA replicons eventually cause lysis of transfected cells and therefore do not raise the concern of integration into the host genome. We evaluated the effect of linking human papillomavirus type 16 E7 as a model Ag to Mycobacterium tuberculosis heat shock protein 70 (HSP70) on the potency of Ag-specific immunity generated by a Sindbis virus self-replicating RNA vector, SINrep5. Our results indicated that this RNA replicon Vaccine containing an E7/HSP70 fusion gene generated significantly higher E7-specific T cell-mediated immune responses in vaccinated mice than did Vaccines containing the wild-type E7 gene. Furthermore, our in vitro studies demonstrated that E7 Ag from E7/HSP70 RNA replicon-transfected cells can be processed by bone marrow-derived dendritic cells and presented more efficiently through the MHC class I pathway than can wild-type E7 RNA replicon-transfected cells. More importantly, the fusion of HSP70 to E7 converted a less effective Vaccine into one with significant potency against E7-expressing tumors. This antitumor effect was dependent on NK cells and CD8 + T cells. These results indicated that fusion of HSP70 to an Ag gene may greatly enhance the potency of self-replicating RNA Vaccines.
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enhancement of sindbis virus self replicating RNA Vaccine potency by linkage of herpes simplex virus type 1 vp22 protein to antigen
Journal of Virology, 2001Co-Authors: Wenfang Cheng, Chienfu Hung, Cheeyin Chai, Morris Ling, Liangmai He, Tzyy Choou WuAbstract:Recently, self-replicating and self-limiting RNA Vaccines (RNA replicons) have emerged as an important form of nucleic acid Vaccines. Self-replicating RNA eventually causes lysis of transfected cells and does not raise the concern associated with naked DNA Vaccines of integration into the host genome. This is particularly important for development of Vaccines targeting proteins that are potentially oncogenic. However, the potency of RNA replicons is significantly limited by their lack of intrinsic ability to spread in vivo. The herpes simplex virus type 1 protein VP22 has demonstrated the remarkable property of intercellular transport and provides the opportunity to enhance RNA replicon Vaccine potency. We therefore created a novel fusion of VP22 with a model tumor antigen, human papillomavirus type 16 E7, in a Sindbis virus RNA replicon vector. The linkage of VP22 with E7 resulted in a significant enhancement of E7-specific CD8 + T-cell activities in vaccinated mice and converted a less effective RNA replicon Vaccine into one with significant potency against E7-expressing tumors. These results indicate that fusion of VP22 to an antigen gene may greatly enhance the potency of RNA replicon Vaccines.
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enhancement of sindbis virus self replicating RNA Vaccine potency by targeting antigen to endosomal lysosomal compartments
Human Gene Therapy, 2001Co-Authors: Wenfang Cheng, Chienfu Hung, Cheeyin Chai, Liangmei He, Morris Ling, Leigh A Slater, Richard B S Roden, Tzyy Choou WuAbstract:Self-replicating RNA Vaccines (RNA replicons) have emerged as an attractive approach for tumor immunotherapy. RNA replicons do not integrate into host chromosomes, eliminating the concern for oncogenicity associated with a DNA Vaccine. In this study, we used human papillomavirus type 16 (HPV-16) E7 as a model antigen and evaluated E7-specific immunity generated by a Sindbis virus self-replicating RNA vector, SIN-rep5. Three different constructs were created to target E7 antigen to different cellular localizations: (1) E7, a cytosolic/nuclear protein; (2) Sig/E7, a secretory protein; (3) Sig/E7/LAMP-1, in which we linked the transmembrane and cytoplasmic regions of the lysosome-associated membrane protein 1 (LAMP-1) to E7 protein to target E7 to the endosomal/lysosomal compartment. We found that the RNA replicon Vaccine containing the Sig/E7/LAMP-1 fusion gene generated the highest E7-specific T cell-mediated immune responses and antitumor effects relative to RNA Vaccines containing either wild-type E7 or ...
Cheeyin Chai - One of the best experts on this subject based on the ideXlab platform.
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enhancement of sindbis virus self replicating RNA Vaccine potency by linkage of mycobacterium tuberculosis heat shock protein 70 gene to an antigen gene
Journal of Immunology, 2001Co-Authors: Wenfang Cheng, Chienfu Hung, Cheeyin Chai, Morris Ling, Liangmai He, Charles M Rice, Tzyy Choou WuAbstract:Recently, self-replicating RNA Vaccines (RNA replicons) have emerged as an effective strategy for nucleic acid Vaccine development. Unlike naked DNA Vaccines, RNA replicons eventually cause lysis of transfected cells and therefore do not raise the concern of integration into the host genome. We evaluated the effect of linking human papillomavirus type 16 E7 as a model Ag to Mycobacterium tuberculosis heat shock protein 70 (HSP70) on the potency of Ag-specific immunity generated by a Sindbis virus self-replicating RNA vector, SINrep5. Our results indicated that this RNA replicon Vaccine containing an E7/HSP70 fusion gene generated significantly higher E7-specific T cell-mediated immune responses in vaccinated mice than did Vaccines containing the wild-type E7 gene. Furthermore, our in vitro studies demonstrated that E7 Ag from E7/HSP70 RNA replicon-transfected cells can be processed by bone marrow-derived dendritic cells and presented more efficiently through the MHC class I pathway than can wild-type E7 RNA replicon-transfected cells. More importantly, the fusion of HSP70 to E7 converted a less effective Vaccine into one with significant potency against E7-expressing tumors. This antitumor effect was dependent on NK cells and CD8 + T cells. These results indicated that fusion of HSP70 to an Ag gene may greatly enhance the potency of self-replicating RNA Vaccines.
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enhancement of sindbis virus self replicating RNA Vaccine potency by linkage of herpes simplex virus type 1 vp22 protein to antigen
Journal of Virology, 2001Co-Authors: Wenfang Cheng, Chienfu Hung, Cheeyin Chai, Morris Ling, Liangmai He, Tzyy Choou WuAbstract:Recently, self-replicating and self-limiting RNA Vaccines (RNA replicons) have emerged as an important form of nucleic acid Vaccines. Self-replicating RNA eventually causes lysis of transfected cells and does not raise the concern associated with naked DNA Vaccines of integration into the host genome. This is particularly important for development of Vaccines targeting proteins that are potentially oncogenic. However, the potency of RNA replicons is significantly limited by their lack of intrinsic ability to spread in vivo. The herpes simplex virus type 1 protein VP22 has demonstrated the remarkable property of intercellular transport and provides the opportunity to enhance RNA replicon Vaccine potency. We therefore created a novel fusion of VP22 with a model tumor antigen, human papillomavirus type 16 E7, in a Sindbis virus RNA replicon vector. The linkage of VP22 with E7 resulted in a significant enhancement of E7-specific CD8 + T-cell activities in vaccinated mice and converted a less effective RNA replicon Vaccine into one with significant potency against E7-expressing tumors. These results indicate that fusion of VP22 to an antigen gene may greatly enhance the potency of RNA replicon Vaccines.
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enhancement of sindbis virus self replicating RNA Vaccine potency by targeting antigen to endosomal lysosomal compartments
Human Gene Therapy, 2001Co-Authors: Wenfang Cheng, Chienfu Hung, Cheeyin Chai, Liangmei He, Morris Ling, Leigh A Slater, Richard B S Roden, Tzyy Choou WuAbstract:Self-replicating RNA Vaccines (RNA replicons) have emerged as an attractive approach for tumor immunotherapy. RNA replicons do not integrate into host chromosomes, eliminating the concern for oncogenicity associated with a DNA Vaccine. In this study, we used human papillomavirus type 16 (HPV-16) E7 as a model antigen and evaluated E7-specific immunity generated by a Sindbis virus self-replicating RNA vector, SIN-rep5. Three different constructs were created to target E7 antigen to different cellular localizations: (1) E7, a cytosolic/nuclear protein; (2) Sig/E7, a secretory protein; (3) Sig/E7/LAMP-1, in which we linked the transmembrane and cytoplasmic regions of the lysosome-associated membrane protein 1 (LAMP-1) to E7 protein to target E7 to the endosomal/lysosomal compartment. We found that the RNA replicon Vaccine containing the Sig/E7/LAMP-1 fusion gene generated the highest E7-specific T cell-mediated immune responses and antitumor effects relative to RNA Vaccines containing either wild-type E7 or ...
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Enhancement of Sindbis Virus Self-Replicating RNA Vaccine Potency by Targeting Antigen to Endosomal/Lysosomal Compartments
Human Gene Therapy, 2001Co-Authors: Wenfang Cheng, Chienfu Hung, Cheeyin Chai, Liangmei He, Morris Ling, Leigh A Slater, Richard B S Roden, Tzyy Choou WuAbstract:Self-replicating RNA Vaccines (RNA replicons) have emerged as an attractive approach for tumor immunotherapy. RNA replicons do not integrate into host chromosomes, eliminating the concern for oncogenicity associated with a DNA Vaccine. In this study, we used human papillomavirus type 16 (HPV-16) E7 as a model antigen and evaluated E7-specific immunity generated by a Sindbis virus self-replicating RNA vector, SIN-rep5. Three different constructs were created to target E7 antigen to different cellular localizations: (1) E7, a cytosolic/nuclear protein; (2) Sig/E7, a secretory protein; (3) Sig/E7/LAMP-1, in which we linked the transmembrane and cytoplasmic regions of the lysosome-associated membrane protein 1 (LAMP-1) to E7 protein to target E7 to the endosomal/lysosomal compartment. We found that the RNA replicon Vaccine containing the Sig/E7/LAMP-1 fusion gene generated the highest E7-specific T cell-mediated immune responses and antitumor effects relative to RNA Vaccines containing either wild-type E7 or ...
Liangmei He - One of the best experts on this subject based on the ideXlab platform.
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naked RNA Vaccine controls tumors with down regulated mhc class i expression through nk cells and perforin dependent pathways
European Journal of Immunology, 2004Co-Authors: Wenfang Cheng, Chienfu Hung, Liangmei He, Tzyy Choou Wu, Yi Ning Su, Ming Cheng Chang, Chian Chen, Chang Yao HsiehAbstract:One of the major issues facing cancer immunotherapy is that many human cancers down-regulate expression of MHC class I molecules. The understanding of the mechanisms of antitumor effects against tumors with down-regulated MHC class I will facilitate rational design of Vaccines and immunotherapeutic strategies to control such tumors. A naked Sindbis RNA replicon vector (SINrep5) encoding the herpes simplex virus type 1 protein VP22 linked to E7 (SINrep5-VP22/E7) generated significant antitumor effects against TC-1 and TC-1 P3(A15), tumors with down-regulated MHC class I expression. Naked SINrep5 RNA without the insert or an E7 Vaccine also produced antitumor effects against TC-1 P3(A15) but not TC-1. Mice vaccinated with any of these naked RNA Vaccines generated higher percentages of NK cells. In vivo Ab depletion experiments revealed that NK cells were important for the antitumor effects of naked RNA Vaccines against TC-1 P3(A15) and that the antitumor effects were perforin-dependent. Poly I:C also increased the percentage of NK cells and generated antitumor effects against the tumors with down-regulated MHC class I. Thus, the SINrep5-VP22/E7 naked RNA Vaccinecontrols MHC class I-positive and MHC class I-down-regulated tumor cells via different mechanisms, and NK cells play an important role in the antitumor effects generated by naked RNA replicon Vaccines.
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Naked RNA Vaccine controls tumors with down‐regulated MHC class I expression through NK cells and perforin‐dependent pathways
European Journal of Immunology, 2004Co-Authors: Wenfang Cheng, Chienfu Hung, Liangmei He, Tzyy Choou Wu, Yi Ning Su, Ming Cheng Chang, Chian Chen, Chang Yao HsiehAbstract:One of the major issues facing cancer immunotherapy is that many human cancers down-regulate expression of MHC class I molecules. The understanding of the mechanisms of antitumor effects against tumors with down-regulated MHC class I will facilitate rational design of Vaccines and immunotherapeutic strategies to control such tumors. A naked Sindbis RNA replicon vector (SINrep5) encoding the herpes simplex virus type 1 protein VP22 linked to E7 (SINrep5-VP22/E7) generated significant antitumor effects against TC-1 and TC-1 P3(A15), tumors with down-regulated MHC class I expression. Naked SINrep5 RNA without the insert or an E7 Vaccine also produced antitumor effects against TC-1 P3(A15) but not TC-1. Mice vaccinated with any of these naked RNA Vaccines generated higher percentages of NK cells. In vivo Ab depletion experiments revealed that NK cells were important for the antitumor effects of naked RNA Vaccines against TC-1 P3(A15) and that the antitumor effects were perforin-dependent. Poly I:C also increased the percentage of NK cells and generated antitumor effects against the tumors with down-regulated MHC class I. Thus, the SINrep5-VP22/E7 naked RNA Vaccinecontrols MHC class I-positive and MHC class I-down-regulated tumor cells via different mechanisms, and NK cells play an important role in the antitumor effects generated by naked RNA replicon Vaccines.
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enhancement of sindbis virus self replicating RNA Vaccine potency by targeting antigen to endosomal lysosomal compartments
Human Gene Therapy, 2001Co-Authors: Wenfang Cheng, Chienfu Hung, Cheeyin Chai, Liangmei He, Morris Ling, Leigh A Slater, Richard B S Roden, Tzyy Choou WuAbstract:Self-replicating RNA Vaccines (RNA replicons) have emerged as an attractive approach for tumor immunotherapy. RNA replicons do not integrate into host chromosomes, eliminating the concern for oncogenicity associated with a DNA Vaccine. In this study, we used human papillomavirus type 16 (HPV-16) E7 as a model antigen and evaluated E7-specific immunity generated by a Sindbis virus self-replicating RNA vector, SIN-rep5. Three different constructs were created to target E7 antigen to different cellular localizations: (1) E7, a cytosolic/nuclear protein; (2) Sig/E7, a secretory protein; (3) Sig/E7/LAMP-1, in which we linked the transmembrane and cytoplasmic regions of the lysosome-associated membrane protein 1 (LAMP-1) to E7 protein to target E7 to the endosomal/lysosomal compartment. We found that the RNA replicon Vaccine containing the Sig/E7/LAMP-1 fusion gene generated the highest E7-specific T cell-mediated immune responses and antitumor effects relative to RNA Vaccines containing either wild-type E7 or ...
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Enhancement of Sindbis Virus Self-Replicating RNA Vaccine Potency by Targeting Antigen to Endosomal/Lysosomal Compartments
Human Gene Therapy, 2001Co-Authors: Wenfang Cheng, Chienfu Hung, Cheeyin Chai, Liangmei He, Morris Ling, Leigh A Slater, Richard B S Roden, Tzyy Choou WuAbstract:Self-replicating RNA Vaccines (RNA replicons) have emerged as an attractive approach for tumor immunotherapy. RNA replicons do not integrate into host chromosomes, eliminating the concern for oncogenicity associated with a DNA Vaccine. In this study, we used human papillomavirus type 16 (HPV-16) E7 as a model antigen and evaluated E7-specific immunity generated by a Sindbis virus self-replicating RNA vector, SIN-rep5. Three different constructs were created to target E7 antigen to different cellular localizations: (1) E7, a cytosolic/nuclear protein; (2) Sig/E7, a secretory protein; (3) Sig/E7/LAMP-1, in which we linked the transmembrane and cytoplasmic regions of the lysosome-associated membrane protein 1 (LAMP-1) to E7 protein to target E7 to the endosomal/lysosomal compartment. We found that the RNA replicon Vaccine containing the Sig/E7/LAMP-1 fusion gene generated the highest E7-specific T cell-mediated immune responses and antitumor effects relative to RNA Vaccines containing either wild-type E7 or ...
