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      Advances in Lipid Nanoparticles for mRNA-Based Cancer Immunotherapy

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          Abstract

          Over 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.

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          mRNA vaccines — a new era in vaccinology

          Norbert Pardi, Michael Hogan, Frederick W. Porter … (2018)
          mRNA vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. However, their application has until recently been restricted by the instability and inefficient in vivo delivery of mRNA. Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated encouraging results in both animal models and humans. This Review provides a detailed overview of mRNA vaccines and considers future directions and challenges in advancing this promising vaccine platform to widespread therapeutic use.
          Article 0 comments Cited 1487 times – based on 0 reviews     Review now
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            Principles of nanoparticle design for overcoming biological barriers to drug delivery.

            Elvin Blanco, Haifa Shen, Mauro Ferrari (2015)
            Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.
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              mRNA-based therapeutics--developing a new class of drugs.

              Ugur Sahin, Katalin Karikó, Özlem Türeci (2014)
              In vitro transcribed (IVT) mRNA has recently come into focus as a potential new drug class to deliver genetic information. Such synthetic mRNA can be engineered to transiently express proteins by structurally resembling natural mRNA. Advances in addressing the inherent challenges of this drug class, particularly related to controlling the translational efficacy and immunogenicity of the IVTmRNA, provide the basis for a broad range of potential applications. mRNA-based cancer immunotherapies and infectious disease vaccines have entered clinical development. Meanwhile, emerging novel approaches include in vivo delivery of IVT mRNA to replace or supplement proteins, IVT mRNA-based generation of pluripotent stem cells and genome engineering using IVT mRNA-encoded designer nucleases. This Review provides a comprehensive overview of the current state of mRNA-based drug technologies and their applications, and discusses the key challenges and opportunities in developing these into a new class of drugs.
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Chem
                Journal ID (iso-abbrev): Front Chem
                Journal ID (publisher-id): Front. Chem.
                Title: Frontiers in Chemistry
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 2296-2646
                Publication date (Electronic): 23 October 2020
                Publication date Collection: 2020
                Volume: 8
                Electronic Location Identifier: 589959
                Affiliations
                [1] 1Barts Cancer Institute, Queen Mary University of London , London, United Kingdom
                [2] 2Department Matematica e Fisica 'Ennio De Giorgi', Università del Salento , Lecce, Italy
                [3] 3Nanomaterials for Biomedical Applications, Istituto Italiano di Tecnologia (IIT) , Genova, Italy
                Author notes

                Edited by: Alan Talevi, National University of La Plata, Argentina

                Reviewed by: Kyeongsoon Park, Chung-Ang University, South Korea; Zhenjun Yang, Peking University, China

                *Correspondence: Stefano Persano stefano.persano@ 123456iit.it

                This article was submitted to Medicinal and Pharmaceutical Chemistry, a section of the journal Frontiers in Chemistry

                Article
                DOI: 10.3389/fchem.2020.589959
                PMC ID: 7645050
                SO-VID: ea55ff99-919f-4753-b267-4fe18d4bc2fd
                Copyright © Copyright © 2020 Guevara, Persano and Persano.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 31 July 2020
                Date accepted : 16 September 2020
                Page count
                Figures: 6, Tables: 2, Equations: 0, References: 97, Pages: 17, Words: 12612
                Categories
                Subject: Chemistry
                Subject: Review

                Keywords: monoclonal antibodies,car t cells,cancer vaccines,lipid nanoparticles,therapeutic mrna,cancer immunotherapy
                Data availability:
                Keywords: monoclonal antibodies, car t cells, cancer vaccines, lipid nanoparticles, therapeutic mrna, cancer immunotherapy

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