Enhancement of immunotherapeutic effects of HPV16E7 on cervical cancer by fusion with CTLA4 extracellular region

Zheng, Yi; Zhang, Yijuan; Ma, Yuandong; Wan, Jun; Shi, Chunyi; Huang, Laiqiang

doi:10.1007/s12275-008-0087-1

Cited by 14 publications

(14 citation statements)

References 34 publications

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“…2). These properties have not been reported previously for any DC-targeted vaccine containing HPVE7 antigens 23,26 and represent a major improvement over other targeting moieties. Indeed, it has been shown that when DCs fail to mature after taking up the antigen the outcome may be tolerance rather than immunity.…”

Section: Discussionmentioning

confidence: 58%

Eradication of large tumors expressing human papillomavirus E7 protein by therapeutic vaccination with E7 fused to the extra domain a from fibronectin

Mansilla¹,

Berraondo²,

Durantez³

et al. 2011

Intl Journal of Cancer

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Cervical carcinoma is one of the most common cancers in women worldwide. It is well established that chronic infection of the genital tract by various mucosatropic human papillomavirus (HPV) types causes cervical cancer. Cellular immunity to E7 protein from HPV (HPVE7) has been associated with clinical and cytologic resolution of HPV-induced lesions. Thus, we decided to test if targeting of HPVE7 to dendritic cells using a fusion protein containing the extra domain A (EDA) from fibronectin, a natural ligand for TLR4, and HPVE7 (EDA-HPVE7) might be an efficient vaccine for the treatment of cervical carcinoma. We found that EDA-HPVE7 fusion protein was efficiently captured by bone marrow derived dendritic cells in vitro and induced their maturation, with the upregulation of maturation markers and the production of IL-12. Immunization of mice with EDA-HPVE7 fusion protein induced antitumor CD8 1 T cell responses in the absence of additional adjuvants. Repeated intratumoral administration of EDA-HPVE7 in saline was able to cure established TC-1 tumors of 5-7 mm in diameter. More importantly, intravenous injection with EDA-HPVE7 in combination with the TLR ligand polyinosinic-polycytidylic acid (pIC), or with low doses of cyclophosphamide and the TLR9 ligand CpG-B complexed in cationic lipids, were able to eradicate large established TC-1 tumors (1.2 cm in diameter). Thus, therapeutic vaccination with EDA-HPVE7 fusion protein may be effective in the treatment of human cervical carcinoma.There is consistent evidence that chronic infection of the genital tract by various mucosatropic human papillomavirus (HPV) types cause cervical cancer. 1 In contrast to the prophylactic HPV vaccines that exhibit great promise in reducing the burden of cervical cancer, there is limited progress towards the development of immune therapeutic strategies for those women already infected with HPV who do not benefit from the current vaccines. The efficacy of these HPV vaccines correlates with the presence of serum neutralizing antibodies which may prevent virus infection (reviewed in ref. 2). However, it is believed that T cell immune responses, in particular against E7 protein, may play an important role in viral clearance and resolution of HPV-induced lesions. 3 Thus, a vaccination strategy able to activate a strong T cell immune response with the capacity to recognize and kill cancer cells expressing HPV proteins might be considered as therapeutic alternative for cervical carcinoma.Dendritic cells (DCs) are considered to be at the centre of acquired T cell responses due to their outstanding ability to capture antigens (Ag) and process them for their presentation as short peptides in the context of MHC molecules to naïve T cells. The unique capacity of DC to elicit immune responses has prompted many laboratories to use DC in clinical trials. However, ex vivo manipulation of DC for the production of DC-based vaccines is expensive, time consuming and difficult to standardize. Indeed, several variables, such as DC lineage, antigen loading to...

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Section: Discussionmentioning

confidence: 58%

Eradication of large tumors expressing human papillomavirus E7 protein by therapeutic vaccination with E7 fused to the extra domain a from fibronectin

Mansilla¹,

Berraondo²,

Durantez³

et al. 2011

Intl Journal of Cancer

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“…2). These properties have not been reported previously for any DC‐targeted vaccine containing HPVE7 antigens23, 26 and represent a major improvement over other targeting moieties. Indeed, it has been shown that when DCs fail to mature after taking up the antigen the outcome may be tolerance rather than immunity 6, 8, 10, 27.…”

Section: Discussionmentioning

confidence: 59%

Influence of processing conditions on the morphological and mechanical properties of compatibilized PP/LCP blends

Filipe

Maia

Leal

et al. 2007

J of Applied Polymer Sci

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ABSTRACT:The main aim of this work is to study the influence of the application of different processing conditions on the morphological and mechanical properties of thermoplastic/LCP blends, in which the viscosity ratios are inferior to unity and decrease with increasing temperature. The way the microstructure evolves along the extruder determines the final morphology and thus, the mechanical performance of the systems. In the present case, the mechanical properties are related with the degree of fibrillation in the final composites. The best degree of fibrillation was obtained for low screw speeds and temperatures and for intermediate outputs. The use of high screw speeds and processing temperatures results in a decrease of the viscosity ratio, in the former case via an increase in the viscous dissipation, at the regions of higher shear rates (kneading-elements). The application of a lower processing temperature is advantageous for deformation, break-up, and fibrillar formation because of the higher viscosity ratios and higher shear stresses involved.

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“…The culture supernatants were lyophilized and resuspended in 300 µL of PBS. The levels of IFN-γ in culture supernatant of mice lymphocytes that were immunized with HCV1b-E2 protein and HCV1b-E2-PLGA microspheres were compared using the IFN-γ ELISA kit 25 (Dakewe Biotech Co. Ltd., Beijing, People's Republic of China) according to the manufacturer's instructions. Mice IFN-γ standard proteins at 40, 20, 10, and 5 pg were measured as the standard point of OD at 450 nm.…”

Section: Ifn-γ Elisa Assaymentioning

confidence: 99%

Hepatitis C virus E2 protein encapsulation into poly D, L-lactic-<em>co</em>-glycolide microspheres could induce mice cytotoxic T-cell response

Roopngam¹,

Liu²,

Mei³

et al. 2016

IJN

Self Cite

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Hepatitis C virus (HCV) is known to cause hepatitis and hepatocellular carcinoma. E2 envelope glycoprotein of HCV type (HCV-E2) has been reported to bind human host cells and is a major target for developing anti-HCV vaccines. However, the therapeutic vaccine for infected patients still needs further development. The vaccine aims to provide cytotoxic T-cells to eliminate infected cells and hepatocellular carcinoma. Currently, there is no effective HCV therapeutic vaccine because most chronically infected patients rarely generate cytotoxic T-cells, even though they have high levels of neutralizing antibodies. Therefore, the adjuvant must be applied to enhance the efficacy of the therapeutic vaccine. In this study, we constructed HCV1b-E2 recombinant protein, a truncated form of peptide, to combine with an effective vaccine adjuvant and delivery system by using poly d , l -lactic- co -glycolide (PLGA) microspheres. HCV1b-E2 protein was effectively encapsulated into PLGA microspheres (HCV1b-E2-PLGA) as a strategy to deliver an insoluble form of HCV1b-E2 protein. The size and shape of PLGA microspheres were generated properly to carry an insoluble form of viral peptide in vivo. The encapsulated viral protein was slowly and continuously released from PLGA microspheres, which indicated the property of the adjuvant. HCV1b-E2-PLGA can trigger a cell-mediated immune response by inducing an expression of mice CD8 + T-cells. Our results demonstrated that HCV1b-E2-PLGA-immunized mice have a significantly increased CD8 + T-cell number, whereas HCV1b-E2-immunized mice have a lower number of CD8 + T-cells. Moreover, HCV1b-E2-PLGA could induce a specific antibody to viral protein, and the immune cells could secrete IFN-γ, which is a significant cytokine for viral response. Thus, HCV1b-E2-PLGA is shown to have adjuvant property and efficacy in the murine model, which is a good strategy to develop HCV prophylactic and therapeutic vaccines.

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Enhancement of immunotherapeutic effects of HPV16E7 on cervical cancer by fusion with CTLA4 extracellular region

Cited by 14 publications

References 34 publications

Eradication of large tumors expressing human papillomavirus E7 protein by therapeutic vaccination with E7 fused to the extra domain a from fibronectin

Eradication of large tumors expressing human papillomavirus E7 protein by therapeutic vaccination with E7 fused to the extra domain a from fibronectin

Influence of processing conditions on the morphological and mechanical properties of compatibilized PP/LCP blends

Hepatitis C virus E2 protein encapsulation into poly D, L-lactic-<em>co</em>-glycolide microspheres could induce mice cytotoxic T-cell response

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Enhancement of immunotherapeutic effects of HPV16E7 on cervical cancer by fusion with CTLA4 extracellular region

Cited by 14 publications

References 34 publications

Eradication of large tumors expressing human papillomavirus E7 protein by therapeutic vaccination with E7 fused to the extra domain a from fibronectin

Eradication of large tumors expressing human papillomavirus E7 protein by therapeutic vaccination with E7 fused to the extra domain a from fibronectin

Influence of processing conditions on the morphological and mechanical properties of compatibilized PP/LCP blends

Hepatitis C virus E2 protein encapsulation into poly D, L-lactic-<em>co</em>-glycolide&nbsp;microspheres could induce mice cytotoxic T-cell response

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Hepatitis C virus E2 protein encapsulation into poly D, L-lactic-<em>co</em>-glycolide microspheres could induce mice cytotoxic T-cell response