The Experts below are selected from a list of 20367 Experts worldwide ranked by ideXlab platform
Vito Michele Fazio - One of the best experts on this subject based on the ideXlab platform.
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Application of Electroporation in DNA Vaccination Protocols
Current Gene Therapy, 2010Co-Authors: Pieranna Chiarella, Vito Michele Fazio, Emanuela SignoriAbstract:Vaccination is historically one of the most important methods for preventing infectious diseases in humans and animals. Due to recent advances in understanding the biology of the immune system, a more rational design of vaccines and Vaccination strategies such as those based on gene transfer has been proposed. In particular, naked DNA Vaccination is emerging as a promising approach for introducing foreign antigens into the host, inducing protective immunity against infectious diseases and malignant tumours. Plasmid DNA vaccines offer several advantages in comparison to traditional vaccines such as safety, tolerability and feasibility in manufacture. Nevertheless, because of their poor immunogenicity, plasmid DNA vaccines need further implementation. Recent data suggest electroporation as a useful strategy to improve DNA-based Vaccination protocols, being able to stimulate both the humoural and cellular immune responses. In preclinical trials, electroporation is successfully used in prime-boost combination protocols and its efficacy and tolerability have been demonstrated in Phase I clinical trials. Since these initial results appear promising, in the next future we will assist further developments of naked DNA Vaccination associated to the electroporation technology. This approach not only provides the basis for human studies but also a practical application to veterinary medicine.
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DNA Vaccination strategies for anti-tumour effective gene therapy protocols.
Cancer Immunology Immunotherapy, 2010Co-Authors: Emanuela Signori, Sandra Iurescia, Emanuela Massi, Daniela Fioretti, Pieranna Chiarella, Mariangela De Robertis, Monica Rinaldi, Giancarlo Tonon, Vito Michele FazioAbstract:After more than 15 years of experimentation, DNA vaccines have become a promising perspective for tumour diseases, and animal models are widely used to study the biological features of human cancer progression and to test the efficacy of Vaccination protocols. In recent years, immunisation with naked plasmid DNA encoding tumour-associated antigens or tumour-specific antigens has revealed a number of advantages: antigen-specific DNA Vaccination stimulates both cellular and humoral immune responses; multiple or multi-gene vectors encoding several antigens/determinants and immune-modulatory molecules can be delivered as single administration; DNA Vaccination does not induce autoimmune disease in normal animals; DNA vaccines based on plasmid vectors can be produced and tested rapidly and economically. However, DNA vaccines have shown low immunogenicity when tested in human clinical trials, and compared with traditional vaccines, they induce weak immune responses. Therefore, the improvement of vaccine efficacy has become a critical goal in the development of effective DNA Vaccination protocols for anti-tumour therapy. Several strategies are taken into account for improving the DNA Vaccination efficacy, such as antigen optimisation, use of adjuvants and delivery systems like electroporation, co-expression of cytokines and co-stimulatory molecules in the same vector, different Vaccination protocols. In this review we discuss how the combination of these approaches may contribute to the development of more effective DNA Vaccination protocols for the therapy of lymphoma in a mouse model.
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Strategies for effective naked-DNA Vaccination against infectious diseases.
Recent Patents on Anti-Infective Drug Discovery, 2008Co-Authors: Pieranna Chiarella, Emanuela Massi, Mariangela De Robertis, Vito Michele Fazio, Emanuela SignoriAbstract:To date, Vaccination is an active area of investigation for its application to a great variety of human diseases including infections and cancer. In particular, naked-DNA Vaccination has arisen as effective strategy in the preventive medicine field with promising future prospects. The ability of plasmid DNA to activate the humoural and the cellular arms of the immune system against the encoded antigen have resulted in intensive study of new strategies aimed at increasing the DNA vaccine immunogenicity. Nevertheless, plasmid-based vaccines emerged as a safer and advantageous alternative with respect to viral vector vaccines. Recent advances in both the immunological and biotechnological research field made it possible to enhance significantly the DNA vaccine potency. Most of these approaches are based on both the discovery of novel delivery systems and the implementation of plasmid constructs, achieved through genetic engineering. In this review, we will describe some of the most relevant patents issued in the last ten years, supporting the progress made in naked-DNA Vaccination against infectious diseases.
Emanuela Signori - One of the best experts on this subject based on the ideXlab platform.
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Application of Electroporation in DNA Vaccination Protocols
Current Gene Therapy, 2010Co-Authors: Pieranna Chiarella, Vito Michele Fazio, Emanuela SignoriAbstract:Vaccination is historically one of the most important methods for preventing infectious diseases in humans and animals. Due to recent advances in understanding the biology of the immune system, a more rational design of vaccines and Vaccination strategies such as those based on gene transfer has been proposed. In particular, naked DNA Vaccination is emerging as a promising approach for introducing foreign antigens into the host, inducing protective immunity against infectious diseases and malignant tumours. Plasmid DNA vaccines offer several advantages in comparison to traditional vaccines such as safety, tolerability and feasibility in manufacture. Nevertheless, because of their poor immunogenicity, plasmid DNA vaccines need further implementation. Recent data suggest electroporation as a useful strategy to improve DNA-based Vaccination protocols, being able to stimulate both the humoural and cellular immune responses. In preclinical trials, electroporation is successfully used in prime-boost combination protocols and its efficacy and tolerability have been demonstrated in Phase I clinical trials. Since these initial results appear promising, in the next future we will assist further developments of naked DNA Vaccination associated to the electroporation technology. This approach not only provides the basis for human studies but also a practical application to veterinary medicine.
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DNA Vaccination strategies for anti-tumour effective gene therapy protocols.
Cancer Immunology Immunotherapy, 2010Co-Authors: Emanuela Signori, Sandra Iurescia, Emanuela Massi, Daniela Fioretti, Pieranna Chiarella, Mariangela De Robertis, Monica Rinaldi, Giancarlo Tonon, Vito Michele FazioAbstract:After more than 15 years of experimentation, DNA vaccines have become a promising perspective for tumour diseases, and animal models are widely used to study the biological features of human cancer progression and to test the efficacy of Vaccination protocols. In recent years, immunisation with naked plasmid DNA encoding tumour-associated antigens or tumour-specific antigens has revealed a number of advantages: antigen-specific DNA Vaccination stimulates both cellular and humoral immune responses; multiple or multi-gene vectors encoding several antigens/determinants and immune-modulatory molecules can be delivered as single administration; DNA Vaccination does not induce autoimmune disease in normal animals; DNA vaccines based on plasmid vectors can be produced and tested rapidly and economically. However, DNA vaccines have shown low immunogenicity when tested in human clinical trials, and compared with traditional vaccines, they induce weak immune responses. Therefore, the improvement of vaccine efficacy has become a critical goal in the development of effective DNA Vaccination protocols for anti-tumour therapy. Several strategies are taken into account for improving the DNA Vaccination efficacy, such as antigen optimisation, use of adjuvants and delivery systems like electroporation, co-expression of cytokines and co-stimulatory molecules in the same vector, different Vaccination protocols. In this review we discuss how the combination of these approaches may contribute to the development of more effective DNA Vaccination protocols for the therapy of lymphoma in a mouse model.
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Strategies for effective naked-DNA Vaccination against infectious diseases.
Recent Patents on Anti-Infective Drug Discovery, 2008Co-Authors: Pieranna Chiarella, Emanuela Massi, Mariangela De Robertis, Vito Michele Fazio, Emanuela SignoriAbstract:To date, Vaccination is an active area of investigation for its application to a great variety of human diseases including infections and cancer. In particular, naked-DNA Vaccination has arisen as effective strategy in the preventive medicine field with promising future prospects. The ability of plasmid DNA to activate the humoural and the cellular arms of the immune system against the encoded antigen have resulted in intensive study of new strategies aimed at increasing the DNA vaccine immunogenicity. Nevertheless, plasmid-based vaccines emerged as a safer and advantageous alternative with respect to viral vector vaccines. Recent advances in both the immunological and biotechnological research field made it possible to enhance significantly the DNA vaccine potency. Most of these approaches are based on both the discovery of novel delivery systems and the implementation of plasmid constructs, achieved through genetic engineering. In this review, we will describe some of the most relevant patents issued in the last ten years, supporting the progress made in naked-DNA Vaccination against infectious diseases.
Pavel Pisa - One of the best experts on this subject based on the ideXlab platform.
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DNA Vaccination for prostate cancer.
Methods in molecular biology (Clifton N.J.), 2008Co-Authors: Anna-karin Roos, Alan King, Pavel PisaAbstract:DNA-based cancer vaccines have been used successfully in mice to induce cytotoxic T lymphocytes (CTLs) specific for prostate antigens. Translation of a prostate-specific antigen (PSA) DNA vaccine into a phase I clinical trial demonstrated that PSA-specific immune responses could be induced but at a significantly lower level compared with those in mice. To enhance the efficacy of DNA Vaccination against prostate cancer, we have explored and optimized intradermal electroporation as an effective way of delivering a PSA DNA vaccine. The results demonstrated that intradermal DNA Vaccination using low amounts of DNA, followed by two sets of electrical pulses of different length and voltage, effectively induced PSA-specific T cells. Here we describe in detail how to perform intradermal DNA electroporation to induce high gene expression in skin and, more important, how to induce and analyze PSA-specific T cell responses.
Chien-fu Hung - One of the best experts on this subject based on the ideXlab platform.
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treatment with imiquimod enhances antitumor immunity induced by therapeutic hpv DNA Vaccination
Journal of Biomedical Science, 2010Co-Authors: Archana Monie, Chi Mu Chuang, Chien-fu HungAbstract:There is an urgent need to develop new innovative therapies for the control of advanced cancer. The combination of antigen-specific immunotherapy with the employment of immunomodulatory agents has emerged as a potentially plausible approach for the control of advanced cancer. In the current study, we explored the combination of the DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 (HPV-16) E7 antigen (CRT/E7) with the TLR7 agonist imiquimod for their ability to generate E7-specific immune responses and antitumor effects in tumor-bearing mice. We observed that treatment with CRT/E7 DNA in combination with imiquimod leads to an enhancement in the E7-specific CD8+ T cell immune responses and a decrease in the number of myeloid-derived suppressor cells in the tumor microenvironment of tumor-bearing mice. Furthermore, treatment with CRT/E7 DNA in combination with imiquimod leads to significantly improved antitumor effects and prolonged survival in treated mice. In addition, treatment with imiquimod led to increased number of NK1.1+ cells and F4/80+ cells in the tumor microenvironment. Macrophages and NK1.1+ cells were found to play an important role in the antitumor effects mediated by treatment with CRT/E7 DNA in combination with imiquimod. Thus, our data suggests that the combination of therapeutic HPV DNA Vaccination with topical treatment with the TLR7 agonist imiquimod enhances the antitumor immunity induced by DNA Vaccination. The current study has significant implications for future clinical translation.
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Low-dose radiation enhances therapeutic HPV DNA Vaccination in tumor-bearing hosts
Cancer Immunology Immunotherapy, 2008Co-Authors: Chih Wen Tseng, Cornelia L. Trimble, Qi Zeng, Archana Monie, Ronald D. Alvarez, Warner K. Huh, Talia Hoory, Mei Cheng Wang, Chien-fu HungAbstract:Current therapeutic approaches to treatment of patients with bulky cervical cancer are based on conventional in situ ablative modalities including cisplatin-based chemotherapy and radiation therapy. The 5-year survival of patients with nonresectable disease is dismal. Because over 99% of squamous cervical cancer is caused by persistent infection with an oncogenic strain of human papillomavirus (HPV), particularly type 16 and viral oncoproteins E6 and E7 are functionally required for disease initiation and persistence, HPV-targeted immune strategies present a compelling opportunity in which to demonstrate proof of principle. Sublethal doses of radiation and chemotherapeutic agents have been shown to have synergistic effect in combination with either Vaccination against cancer-specific antigens, or with passive transfer of tumor-specific cytotoxic T lymphocytes (CTLs). Here, we explored the combination of low-dose radiation therapy with DNA Vaccination with calreticulin (CRT) linked to the mutated form of HPV-16 E7 antigen (E7(detox)), CRT/E7(detox) in the treatment of E7-expressing TC-1 tumors. We observed that TC-1 tumor-bearing mice treated with radiotherapy combined with CRT/E7(detox) DNA Vaccination generated significant therapeutic antitumor effects and the highest frequency of E7-specific CD8+ T cells in the tumors and spleens of treated mice. Furthermore, treatment with radiotherapy was shown to render the TC-1 tumor cells more susceptible to lysis by E7-specific CTLs. In addition, we observed that treatment with radiotherapy during the second DNA Vaccination generated the highest frequency of E7-specific CD8+ T cells in the tumors and spleens of TC-1 tumor-bearing mice. Finally, TC-1 tumor-bearing mice treated with the chemotherapy in combination with radiation and CRT/E7(detox) DNA Vaccination generate significantly enhanced therapeutic antitumor effects. The clinical implications of the study are discussed.
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Epigallocatechin-3-Gallate Enhances CD8+ T Cell–Mediated Antitumor Immunity Induced by DNA Vaccination
Cancer Research, 2007Co-Authors: Tae Heung Kang, Cornelia L. Trimble, Chien-fu Hung, Jin Hyup Lee, Chung Kil Song, Hee Dong Han, Byung Cheol Shin, Sara I. Pai, Jong-seok Lim, Tae Woo KimAbstract:Immunotherapy and chemotherapy are generally effective against small tumors in animal models of cancer. However, these treatment regimens are generally ineffective against large, bulky tumors. We have found that a multimodality treatment regimen using DNA Vaccination in combination with chemotherapeutic agent epigallocatechin-3-gallate (EGCG), a compound found in green tea, is effective in inhibiting large tumor growth. EGCG was found to induce tumor cellular apoptosis in a dose-dependent manner. The combination of EGCG and DNA Vaccination led to an enhanced tumor-specific T-cell immune response and enhanced antitumor effects, resulting in a higher cure rate than either immunotherapy or EGCG alone. In addition, combined DNA Vaccination and oral EGCG treatment provided long-term antitumor protection in cured mice. Cured animals rejected a challenge of E7-expressing tumors, such as TC-1 and B16E7, but not a challenge of B16 7 weeks after the combined treatment, showing antigen-specific immune responses. These results suggest that multimodality treatment strategies, such as combining immunotherapy with a tumor-killing cancer drug, may be a more effective anticancer strategy than single-modality treatments.
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epigallocatechin 3 gallate enhances cd8 t cell mediated antitumor immunity induced by DNA Vaccination
Cancer Research, 2007Co-Authors: Tae Heung Kang, Cornelia L. Trimble, Chien-fu Hung, Jin Hyup Lee, Chung Kil Song, Hee Dong Han, Byung Cheol Shin, Sara I. Pai, Jong-seok Lim, Tae Woo KimAbstract:Immunotherapy and chemotherapy are generally effective against small tumors in animal models of cancer. However, these treatment regimens are generally ineffective against large, bulky tumors. We have found that a multimodality treatment regimen using DNA Vaccination in combination with chemotherapeutic agent epigallocatechin-3-gallate (EGCG), a compound found in green tea, is effective in inhibiting large tumor growth. EGCG was found to induce tumor cellular apoptosis in a dose-dependent manner. The combination of EGCG and DNA Vaccination led to an enhanced tumor-specific T-cell immune response and enhanced antitumor effects, resulting in a higher cure rate than either immunotherapy or EGCG alone. In addition, combined DNA Vaccination and oral EGCG treatment provided long-term antitumor protection in cured mice. Cured animals rejected a challenge of E7-expressing tumors, such as TC-1 and B16E7, but not a challenge of B16 7 weeks after the combined treatment, showing antigen-specific immune responses. These results suggest that multimodality treatment strategies, such as combining immunotherapy with a tumor-killing cancer drug, may be a more effective anticancer strategy than single-modality treatments.
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A rapid and potent DNA Vaccination strategy defined by in vivo monitoring of antigen expression.
Nature Medicine, 2005Co-Authors: Adriaan D. Bins, Ton N. M. Schumacher, Chien-fu Hung, Annelies Jorritsma, Monika C. Wolkers, John B. A. G. HaanenAbstract:Induction of immunity after DNA Vaccination is generally considered a slow process. Here we show that DNA delivery to the skin results in a highly transient pulse of antigen expression. Based on this information, we developed a new rapid and potent intradermal DNA Vaccination method. By short-interval intradermal DNA delivery, robust T-cell responses, of a magnitude sufficient to reject established subcutaneous tumors, are generated within 12 d. Moreover, this Vaccination strategy confers protecting humoral immunity against influenza A infection within 2 weeks after the start of Vaccination. The strength and speed of this newly developed strategy will be beneficial in situations in which immunity is required in the shortest possible time.
John B. A. G. Haanen - One of the best experts on this subject based on the ideXlab platform.
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DNA Vaccination in Oncology: Current Status, Opportunities and Perspectives
Current Clinical Pharmacology, 2010Co-Authors: Joost H. Van Den Berg, Bastiaan Nuijen, Jos H. Beijnen, Koen Oosterhuis, John B. A. G. HaanenAbstract:After almost 20 years of research, DNA Vaccination is still a relatively young technique in the vaccine-toolbox. DNA vaccines can easily be modified by conventional cloning techniques, are relatively easy to produce and might be particularly useful for therapeutic Vaccination against intracellular pathogens and cancer. After the early pre-clinical successes, DNA Vaccination moved into the clinic and numerous trials have been performed thus far. In the oncology field, these trials aimed for the induction of cellular immunity directed against tumor specific antigens. Although DNA vaccines proved to be well tolerated, and elicited some immune activation in patients, robust immune activation followed by clinical responses has not been observed yet. Nevertheless, several promising strategies are currently under development to increase the performance of the current generation DNA vaccines. Future research has to demonstrate whether these strategies are able to give DNA Vaccination a defined position in cancer treatment.
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Synthetic vehicles for DNA Vaccination.
Journal of Drug Targeting, 2009Co-Authors: Joost H. Van Den Berg, Bastiaan Nuijen, Ton N. M. Schumacher, John B. A. G. Haanen, Gert Storm, Jos H. Beijnen, Wim E. HenninkAbstract:DNA Vaccination is an attractive immunization method able to induce robust cellular immune responses in pre-clinical models. However, clinical DNA Vaccination trials performed thus far have resulted in marginal responses. Consequently, strategies are currently under development to improve the efficacy of DNA vaccines. A promising strategy is the use of synthetic particle formulations as carrier systems for DNA vaccines. This review discusses commonly used synthetic carriers for DNA Vaccination and provides an overview of in vivo studies that use this strategy. Future recommendations on particle characteristics, target cell types and evaluation models are suggested for the potential improvement of current and novel particle delivery systems. Finally, hurdles which need to be tackled for clinical evaluation of these systems are discussed.
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A rapid and potent DNA Vaccination strategy defined by in vivo monitoring of antigen expression.
Nature Medicine, 2005Co-Authors: Adriaan D. Bins, Ton N. M. Schumacher, Chien-fu Hung, Annelies Jorritsma, Monika C. Wolkers, John B. A. G. HaanenAbstract:Induction of immunity after DNA Vaccination is generally considered a slow process. Here we show that DNA delivery to the skin results in a highly transient pulse of antigen expression. Based on this information, we developed a new rapid and potent intradermal DNA Vaccination method. By short-interval intradermal DNA delivery, robust T-cell responses, of a magnitude sufficient to reject established subcutaneous tumors, are generated within 12 d. Moreover, this Vaccination strategy confers protecting humoral immunity against influenza A infection within 2 weeks after the start of Vaccination. The strength and speed of this newly developed strategy will be beneficial in situations in which immunity is required in the shortest possible time.