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  1. Article ; Online: Approaches towards biomaterial-mediated gene editing for cancer immunotherapy.

    Shannon, Sydney R / Ben-Akiva, Elana / Green, Jordan J

    Biomaterials science

    2022  Volume 10, Issue 23, Page(s) 6675–6687

    Abstract: Gene therapies are transforming treatment modalities for many human diseases and disorders, including those in ophthalmology, oncology, and nephrology. To maximize the clinical efficacy and safety of these treatments, consideration of both delivery ... ...

    Abstract Gene therapies are transforming treatment modalities for many human diseases and disorders, including those in ophthalmology, oncology, and nephrology. To maximize the clinical efficacy and safety of these treatments, consideration of both delivery materials and cargos is critical. In consideration of the former, a large effort has been placed on transitioning away from potentially immunoreactive and toxic viral delivery mechanisms towards safer and highly tunable nonviral delivery mechanisms, including polymeric, lipid-based, and inorganic carriers. This change of paradigm does not come without obstacles, as efficient non-viral delivery is challenging, particularly to immune cells, and has yet to see clinical translation breakthroughs for gene editing. This mini-review describes notable examples of biomaterial-based gene delivery to immune cells, with emphasis on recent
    MeSH term(s) Humans ; Gene Editing ; CRISPR-Cas Systems/genetics ; Biocompatible Materials ; Gene Transfer Techniques ; Immunotherapy ; Neoplasms/genetics ; Neoplasms/therapy
    Chemical Substances Biocompatible Materials
    Language English
    Publishing date 2022-11-22
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2693928-9
    ISSN 2047-4849 ; 2047-4830
    ISSN (online) 2047-4849
    ISSN 2047-4830
    DOI 10.1039/d2bm00806h
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Suprachoroidal gene transfer with nonviral nanoparticles in large animal eyes.

    Shen, Jikui / Lima E Silva, Raquel / Zhang, Mingliang / Luly, Kathryn M / Hackett, Sean F / Tzeng, Stephany Y / Lowmaster, Shirley M / Shannon, Sydney R / Wilson, David R / Green, Jordan J / Campochiaro, Peter A

    Science advances

    2024  Volume 10, Issue 10, Page(s) eadl3576

    Abstract: Suprachoroidal nonviral gene therapy with biodegradable poly(β-amino ester) nanoparticles (NPs) provides widespread expression in photoreceptors and retinal pigmented epithelial (RPE) cells and therapeutic benefits in rodents. Here, we show in a human- ... ...

    Abstract Suprachoroidal nonviral gene therapy with biodegradable poly(β-amino ester) nanoparticles (NPs) provides widespread expression in photoreceptors and retinal pigmented epithelial (RPE) cells and therapeutic benefits in rodents. Here, we show in a human-sized minipig eye that suprachoroidal injection of 50 μl of NPs containing 19.2 μg of GFP expression plasmid caused GFP expression in photoreceptors and RPE throughout the entire eye with no toxicity. Two weeks after injection of 50, 100, or 200 μl, there was considerable within-eye and between-eye variability in expression that was reduced 3 months after injection of 200 μl and markedly reduced after three suprachoroidal injections at different locations around the eye. Reduction of bacterial
    MeSH term(s) Animals ; Humans ; Swine ; Swine, Miniature ; Retina/metabolism ; Plasmids/genetics ; Genetic Therapy/methods ; Nanoparticles
    Language English
    Publishing date 2024-03-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.adl3576
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Polymeric nanoparticle gel for intracellular mRNA delivery and immunological reprogramming of tumors.

    Neshat, Sarah Y / Chan, Chun Hei Ryan / Harris, Jawaun / Zmily, Osamah M / Est-Witte, Savannah / Karlsson, Johan / Shannon, Sydney R / Jain, Manav / Doloff, Joshua C / Green, Jordan J / Tzeng, Stephany Y

    Biomaterials

    2023  Volume 300, Page(s) 122185

    Abstract: Immuno-oncology therapies have been of great interest with the goal of inducing sustained tumor regression, but clinical results have demonstrated the need for improved and widely applicable methods. An antigen-free method of cancer immunotherapy can ... ...

    Abstract Immuno-oncology therapies have been of great interest with the goal of inducing sustained tumor regression, but clinical results have demonstrated the need for improved and widely applicable methods. An antigen-free method of cancer immunotherapy can stimulate the immune system to recruit lymphocytes and produce immunostimulatory factors without prior knowledge of neoantigens, while local delivery reduces the risk of systemic toxicity. To improve the interactions between tumor cells and cytotoxic lymphocytes, a gene delivery nanoparticle platform was engineered to reprogram the tumor microenvironment (TME) in situ to be more immunostimulatory by inducing tumor-associated antigen-presenting cells (tAPCs) to activate cytotoxic lymphocytes against the tumor. Biodegradable, lipophilic poly (beta-amino ester) (PBAE) nanoparticles were synthesized and used to co-deliver mRNA constructs encoding a signal 2 co-stimulatory molecule (4-1BBL) and a signal 3 immuno-stimulatory cytokine (IL-12), along with a nucleic acid-based immunomodulatory adjuvant. Nanoparticles are combined with a thermoresponsive block copolymer for gelation at the injection site for local NP retention at the tumor. The reprogramming nanoparticle gel synergizes with immune checkpoint blockade (ICB) to induce tumor regression and clearance in addition to resistance to tumor rechallenge at a distant site. In vitro and in vivo studies reveal increases in immunostimulatory cytokine production and recruitment of immune cells as a result of the nanoparticles. Intratumoral injection of nanoparticles encapsulating mRNA encoding immunostimulatory agents and adjuvants via an injectable thermoresponsive gel has great translational potential as an immuno-oncology therapy that can be accessible to a wide range of patients.
    MeSH term(s) Humans ; RNA, Messenger/genetics ; Antineoplastic Agents/pharmacology ; Nanoparticles ; Polymers/pharmacology ; Adjuvants, Immunologic/pharmacology ; Neoplasms/therapy ; Interleukin-12 ; Tumor Microenvironment
    Chemical Substances RNA, Messenger ; Antineoplastic Agents ; Polymers ; Adjuvants, Immunologic ; Interleukin-12 (187348-17-0)
    Language English
    Publishing date 2023-05-31
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 603079-8
    ISSN 1878-5905 ; 0142-9612
    ISSN (online) 1878-5905
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2023.122185
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 2371: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Shape matters: Biodegradable anisotropic nanoparticle artificial antigen presenting cells for cancer immunotherapy.

    Ben-Akiva, Elana / Hickey, John W / Meyer, Randall A / Isser, Ariel / Shannon, Sydney R / Livingston, Natalie K / Rhodes, Kelly R / Kosmides, Alyssa K / Warren, Tiarra R / Tzeng, Stephany Y / Schneck, Jonathan P / Green, Jordan J

    Acta biomaterialia

    2023  Volume 160, Page(s) 187–197

    Abstract: Artificial antigen presenting cells are biomimetic particles that recapitulate the signals presented by natural antigen presenting cells in order to stimulate T cells in an antigen-specific manner using an acellular platform. We have engineered an ... ...

    Abstract Artificial antigen presenting cells are biomimetic particles that recapitulate the signals presented by natural antigen presenting cells in order to stimulate T cells in an antigen-specific manner using an acellular platform. We have engineered an enhanced nanoscale biodegradable artificial antigen presenting cell by modulating particle shape to achieve a nanoparticle geometry that allows for increased radius of curvature and surface area for T cell contact. The non-spherical nanoparticle artificial antigen presenting cells developed here have reduced nonspecific uptake and improved circulation time compared both to spherical nanoparticles and to traditional microparticle technologies. Additionally, the anisotropic nanoparticle artificial antigen presenting cells efficiently engage with and activate T cells, ultimately leading to a marked anti-tumor effect in a mouse melanoma model that their spherical counterparts were unable to achieve. STATEMENT OF SIGNIFICANCE: Artificial antigen presenting cells (aAPC) can activate antigen-specific CD8+ T cells but have largely been limited to microparticle-based platforms and ex vivo T cell expansion. Although more amenable to in vivo use, nanoscale aAPC have traditionally been ineffective due to limited surface area available for T cell interaction. In this work, we engineered non-spherical biodegradable nanoscale aAPC to investigate the role of particle geometry and develop a translatable platform for T cell activation. The non-spherical aAPC developed here have increased surface area and a flatter surface for T cell engagement and, therefore, can more effectively stimulate antigen-specific T cells, resulting in anti-tumor efficacy in a mouse melanoma model.
    MeSH term(s) Animals ; Mice ; Antigen-Presenting Cells ; Lymphocyte Activation ; Immunotherapy/methods ; Melanoma/pathology ; Nanoparticles ; Antigens
    Chemical Substances Antigens
    Language English
    Publishing date 2023-02-21
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2173841-5
    ISSN 1878-7568 ; 1742-7061
    ISSN (online) 1878-7568
    ISSN 1742-7061
    DOI 10.1016/j.actbio.2023.02.023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Nanoparticle-based modulation of CD4

    Isser, Ariel / Silver, Aliyah B / Pruitt, Hawley C / Mass, Michal / Elias, Emma H / Aihara, Gohta / Kang, Si-Sim / Bachmann, Niklas / Chen, Ying-Yu / Leonard, Elissa K / Bieler, Joan G / Chaisawangwong, Worarat / Choy, Joseph / Shannon, Sydney R / Gerecht, Sharon / Weber, Jeffrey S / Spangler, Jamie B / Schneck, Jonathan P

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 6086

    Abstract: ... Helper ( ... ...

    Abstract Helper (CD4
    MeSH term(s) Animals ; Antigen-Presenting Cells ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; HLA Antigens ; Humans ; Immunotherapy, Adoptive ; Mice ; Nanoparticles
    Chemical Substances HLA Antigens
    Language English
    Publishing date 2022-10-14
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-33597-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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