262 research outputs found
Nano-immunotherapy: Overcoming tumour immune evasion
No full textImmunotherapy is emerging as a groundbreaking cancer treatment, offering the unprecedented opportunity to effectively treat and in several cases, even cure previously untreatable malignancies. Anti-tumour immunotherapies designed to amplify T cell responses against defined tumour antigens have long been considered effective approaches for cancer treatment. Despite a clear rationale behind such immunotherapies, extensive past efforts were unsuccessful in mediating clinically relevant anti-tumour activity in humans. This is mainly because tumours adopt specific mechanisms to circumvent the host ́s immunity. Emerging data suggest that the full potential of cancer immunotherapy will be only achieved by combining immunotherapies designed to generate or amplify anti-tumour T cell responses with strategies able to impair key tumour immune-evasion mechanisms. However, many approaches aimed to re-shape the tumour immune microenvironment (TIME) are commonly associated with severe systemic toxicity, require frequent administration, and only show modest efficacy in clinical settings. The use of nanodelivery systems is revealing as a valid means to overcome these limitations by improving the targeting efficiency, minimising systemic exposure of immunomodulatory agents, and enabling the development of novel combinatorial immunotherapies. In this review, we examine the emerging field of therapeutic modulation of TIME by the use of nanoparticle-based immunomodulators and potential future directions for TIME-targeting nanotherapies
Advances in Lipid Nanoparticles for mRNA-Based Cancer Immunotherapy
No full textOver the past decade, messenger RNA (mRNA) has emerged as potent and flexible platform for the development of novel effective cancer immunotherapies. Advances in non-viral gene delivery technologies, especially the tremendous progress in lipid nanoparticles' manufacturing, have made possible the implementation of mRNA-based antitumor treatments. Several mRNA-based immunotherapies have demonstrated antitumor effect in preclinical and clinical studies, and marked successes have been achieved most notably by its implementation in therapeutic vaccines, cytokines therapies, checkpoint blockade and chimeric antigen receptor (CAR) cell therapy. In this review, we summarize recent advances in the development of lipid nanoparticles for mRNA-based immunotherapies and their applications in cancer treatment. Finally, we also highlight the variety of immunotherapeutic approaches through mRNA delivery and discuss the main factors affecting transfection efficiency and tropism of mRNA-loaded lipid nanoparticles in vivo
Lipid-based vectors for therapeutic mrna-based anti-cancer vaccines
No full textCancer vaccines have been widely explored as a key tool for effective cancer immunotherapy. Despite a convincing rationale behind cancer vaccines, extensive past efforts were unsuccessful in mediating significantly relevant anti-tumor activity in clinical studies. One of the major reasons for such poor outcome, among others, is the low immunogenicity of more traditional vaccines, such as peptide-, protein-and DNA-based vaccines. Recently, mRNA emerged as a promising alternative to traditional vaccine strategies due to its high immunogenicity, suitability for large-scale and low-cost production, and superior safety profile. However, the clinical application of mRNA-based anti-cancer vaccines has been limited by their instability and inefficient in vivo delivery. Recent technological advances have now largely overcome these issues and lipid-based vectors have demonstrated encouraging results as mRNA vaccine platforms against several types of cancers. This review intends to provide a detailed overview of lipid-based vectors for the development of therapeutic mRNA-based anti-tumor vaccines
Lipid Nanoparticles to Harness the Therapeutic Potential of mRNA for Cancer Treatment
No full textIn recent years, mRNA has become an appealing platform for the development of therapeutic agents both for the prevention and treatment of cancer. Efficient delivery of mRNA into target cells is crucial for fully harnessing its therapeutic potential. However, mRNA possesses structural limitations, including its net negative charge and hydrophilicity, that impede its efficient cellular uptake. Likewise, mRNA is characterized by an intrinsic fragility, resulting in it being a highly instable molecule. Lipid nanoparticles (LNPs) have been successfully used for protecting and delivering mRNA encoding for various therapeutic proteins. This chapter is intended to give a comprehensive overview of the current approaches for mRNA synthesis and LNPs manufacturing. We provide an in-depth analysis of how mRNA technology is revolutionizing the area of cancer immunotherapy, critically reviewing the major fields of application of nanoformulated-mRNA medications and addressing the advantages and drawbacks of each one. Finally, we offer a wide landscape of future possibilities and remaining issues of current mRNA-based therapies
Responsabilità dello Stato per violazione del diritto dell'Unione europea e decorrenza del termine di prescrizione dell'azione risarcitoria
No full textLa protezione internazionale nella più recente giurisprudenza di legittimità
No full textIn virtù dell’esame della più recente giurisprudenza di legittimità l’autrice evidenzia come la tutela dei diritti umani fondamentali, basata sulla piena adesione ai principi costituzionali e sovranazionali in materia, rivesta una rilevanza centrale anche in relazione alle questioni concernenti l’immigrazione e la protezione internazionale.By examining the most recent jurisprudence of legitimacy, the author highlights how the protection of fundamental human rights, based on full adherence to the relevant constitutional and supranational principles, has assumed central importance in matters of immigration and international protection
The three-layer concentric model of glioblastoma: Cancer stem cells, microenvironmental regulation, and therapeutic implications
No full textTumors arising in the central nervous system are thought to originate from a sub-population of cells named cancer stem cells (CSCs) or tumor initiating cells (TICs) that possess an immature phenotype, combined with self-renewal and chemotherapy resistance capacity. Moreover, in the last years, these cells have been identified in particular brain tumor niches fundamental for supporting their characteristics. In this paper, we report studies from many authors demonstrating that hypoxia or the so called hypoxic niche plays a crucial role in controlling CSC molecular and phenotypic profile. We recently investigated the relationship existing between Glioblastoma (GBM) stem cells and their niche, defining the theory of three-concentric layers model for GBM mass. According to this model, GBM stem cells reside preferentially within the hypoxic core of the tumour mass, while more differentiated cells are mainly localized along the peripheral and vascularized part of the tumour. This GBM model provides explanation of the effects mediated by the tumour microenvironment on the phenotypic and molecular regulation of GBM stem cells, describing their spatial distribution in the tumor bulk. Moreover, we discuss the possible clinical implications of the creation of this model for future GBM patient management and novel therapeutic strategies development. Copyright © 2011 Luca Persano et al
La tutela della libertà religiosa nel sistema internazionale di salvaguardia dei diritti fondamentali dell'uomo
No full textSciences Po e la razionalizzazione democratica nella Terza Repubblica francese / Sciences Po and the democratic rationalization in the Third French Republic
No full textThe essay, that is part of a broader research conducted in recent years by the Author on political culture and intellectual world in the French Third Republic, assumes the founding moment of the Faculté Libre de Sciences Politiques in 1872 as the keystone of the republicanism between nineteenth and twentieth centuries. It is in fact the moment of maximum effort in the planning some reform models of public education, basic and higher, which will get figures of forward-thinking intellectuals like Émile Boutmy to attempt to create a University at the same time free from State interference, but able to offering to the the same State an élite ‘scientifically’ trained to politics. Although marked by the lesson of positivism of the time, this devouring aspiration – a utopia for someone – will never be aseptic or neutral with respect to one’s time. So the extraordinary insistence, starting at the program of courses at Sciences Po, on history and the knowledge well anchored in the contemporary time, french and even more european. A contemporaneity of war, ça va sans dire
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