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  1. Article ; Online: An Ionizable Lipid Material with a Vitamin E Scaffold as an mRNA Vaccine Platform for Efficient Cytotoxic T Cell Responses.

    Oyama, Ryotaro / Ishigame, Harumichi / Tanaka, Hiroki / Tateshita, Naho / Itazawa, Moeko / Imai, Ryosuke / Nishiumi, Naomasa / Kishikawa, Jun-Ichi / Kato, Takayuki / Anindita, Jessica / Nishikawa, Yoshifumi / Maeki, Masatoshi / Tokeshi, Manabu / Tange, Kota / Nakai, Yuta / Sakurai, Yu / Okada, Takaharu / Akita, Hidetaka

    ACS nano

    2023  Volume 17, Issue 19, Page(s) 18758–18774

    Abstract: RNA vaccines based on lipid nanoparticles (LNPs) ... ...

    Abstract RNA vaccines based on lipid nanoparticles (LNPs) with
    MeSH term(s) Animals ; Mice ; T-Lymphocytes, Cytotoxic ; CD8-Positive T-Lymphocytes ; Vitamin E/pharmacology ; Vaccines, Synthetic ; mRNA Vaccines ; Antigens ; Ovalbumin ; Nanoparticles ; RNA, Messenger/genetics ; Lipids/pharmacology ; Mice, Inbred C57BL ; Dendritic Cells
    Chemical Substances Vitamin E (1406-18-4) ; Vaccines, Synthetic ; mRNA Vaccines ; Antigens ; Ovalbumin (9006-59-1) ; RNA, Messenger ; Lipids
    Language English
    Publishing date 2023-09-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1936-086X
    ISSN (online) 1936-086X
    DOI 10.1021/acsnano.3c02251
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Modifying Antigen-Encapsulating Liposomes with KALA Facilitates MHC Class I Antigen Presentation and Enhances Anti-tumor Effects.

    Miura, Naoya / Akita, Hidetaka / Tateshita, Naho / Nakamura, Takashi / Harashima, Hideyoshi

    Molecular therapy : the journal of the American Society of Gene Therapy

    2017  Volume 25, Issue 4, Page(s) 1003–1013

    Abstract: For a successful anti-cancer vaccine, antigen presentation on the major histocompatibility complex (MHC) class I is a requirement. To accomplish this, an antigen must be delivered to the cytoplasm by overcoming the endosome/lysosome. We previously ... ...

    Abstract For a successful anti-cancer vaccine, antigen presentation on the major histocompatibility complex (MHC) class I is a requirement. To accomplish this, an antigen must be delivered to the cytoplasm by overcoming the endosome/lysosome. We previously reported that a lipid nanoparticle modified with a KALA peptide (WEAKLAKALAKALAKHLAKALAKALKA), an α-helical cationic peptide, permits the encapsulated pDNA to be efficiently delivered to the cytoplasm in bone marrow-derived dendritic cells (BMDCs). Herein, we report on the use of KALA-modified liposomes as an antigen carrier, in an attempt to induce potent antigen-specific cellular immunity. The subcutaneous injection of KALA-modified ovalbumin (OVA)-encapsulating liposomes (KALA-OVA-LPs) elicited a much more potent OVA-specific cytotoxic T lymphocyte activity and anti-tumor effect in comparison with particles that were modified with octa-arginine (R8), a cell-penetrating peptide (R8-OVA-LPs). In addition, the numbers of OVA-specific CD8
    MeSH term(s) Animals ; Antigen Presentation/immunology ; Antigens/chemistry ; Antigens/immunology ; Cancer Vaccines/immunology ; Cell Line, Tumor ; Cytokines/metabolism ; DNA-Binding Proteins/chemistry ; Dendritic Cells/immunology ; Disease Models, Animal ; Female ; Histocompatibility Antigens Class I/chemistry ; Histocompatibility Antigens Class I/immunology ; Immunization ; Liposomes ; Mice ; Neoplasms/immunology ; Neoplasms/therapy ; Ovalbumin/immunology ; Peptides/chemistry ; T-Lymphocytes, Cytotoxic/immunology
    Chemical Substances Antigens ; Cancer Vaccines ; Cytokines ; DNA-Binding Proteins ; Histocompatibility Antigens Class I ; KALA amphipathic peptide ; Liposomes ; Peptides ; Ovalbumin (9006-59-1)
    Language English
    Publishing date 2017-04-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1016/j.ymthe.2017.01.020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Development of a lipoplex-type mRNA carrier composed of an ionizable lipid with a vitamin E scaffold and the KALA peptide for use as an ex vivo dendritic cell-based cancer vaccine

    Tateshita, Naho / Miura, Naoya / Tanaka, Hiroki / Masuda, Takeshi / Ohtsuki, Sumio / Tange, Kota / Nakai, Yuta / Yoshioka, Hiroki / Akita, Hidetaka

    Journal of controlled release. 2019 Sept. 28, v. 310

    2019  

    Abstract: A dendritic cells (DCs)-based vaccine (DC-vaccine) system is an attractive technology for eliciting antigen-specific immune responses that can protect subjects from infectious diseases and for curing various types of cancers. For the insertion of a ... ...

    Abstract A dendritic cells (DCs)-based vaccine (DC-vaccine) system is an attractive technology for eliciting antigen-specific immune responses that can protect subjects from infectious diseases and for curing various types of cancers. For the insertion of a foreign antigen to DCs, the transfection of an antigen-coding mRNA to the cells is a promising approach. In order to introduce an antigen, a carrier for mRNA transfection is required, since the mRNA molecule per se is unstable in serum-containing medium. We previously reported on an ionizable lipid-like material with vitamin E-scaffolds (ssPalmE) as a material for a lipid nanoparticle (LNP)-based carrier for nucleic acids. In the present study, we report on the development of a lipoplex-type mRNA carrier for use as a DC-vaccine by using a combination of an ssPalmE-LNP and an α-helical cationic peptide “KALA” (ssPalmE-KALA). The transfection of mRNAs complexed with the ssPalmE-KALA achieved a significantly higher protein expression and the production of proinflammatory cytokines from murine bone marrow derived DCs (BMDCs) in comparison with a lipoplex that was prepared with an ssPalm with fatty acid-scaffolds (myristic acid; ssPalmM-KALA). A cellular uptake process and a pH-responsive membrane-destabilization activity cannot explain the preferred protein expression and immune-stimulation caused by the ssPalmE-KALA. Proteomic analyses suggest that transfection with the ssPalmM-KALA stimulates a down-regulatory pathway of translation, while the transfection with the ssPalmE-KALA does not stimulate it. In the vaccination with the BMDCs that were preliminarily transfected with an ovalbumin (OVA)-encoding mRNA elicited the induction OVA specific cytotoxic T-lymphocyte activity in vivo. In parallel, the vaccination induced significant prophylactic anti-tumor effects against a model tumor that stably expressed the OVA protein. Based on the above findings, the ssPalmE-KALA appears to be a potent ex vivo DCs-based RNA vaccine platform.
    Keywords T-lymphocytes ; antigens ; antineoplastic activity ; bone marrow ; cancer vaccines ; cytokines ; cytotoxicity ; dendritic cells ; gene expression regulation ; immune response ; infectious diseases ; messenger RNA ; mice ; models ; myristic acid ; nanoparticles ; neoplasms ; ovalbumin ; protein synthesis ; proteomics ; transfection ; translation (genetics) ; vaccination ; vitamin E
    Language English
    Dates of publication 2019-0928
    Size p. 36-46.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2019.08.002
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Development of a lipoplex-type mRNA carrier composed of an ionizable lipid with a vitamin E scaffold and the KALA peptide for use as an ex vivo dendritic cell-based cancer vaccine.

    Tateshita, Naho / Miura, Naoya / Tanaka, Hiroki / Masuda, Takeshi / Ohtsuki, Sumio / Tange, Kota / Nakai, Yuta / Yoshioka, Hiroki / Akita, Hidetaka

    Journal of controlled release : official journal of the Controlled Release Society

    2019  Volume 310, Page(s) 36–46

    Abstract: A dendritic cells (DCs)-based vaccine (DC-vaccine) system is an attractive technology for eliciting antigen-specific immune responses that can protect subjects from infectious diseases and for curing various types of cancers. For the insertion of a ... ...

    Abstract A dendritic cells (DCs)-based vaccine (DC-vaccine) system is an attractive technology for eliciting antigen-specific immune responses that can protect subjects from infectious diseases and for curing various types of cancers. For the insertion of a foreign antigen to DCs, the transfection of an antigen-coding mRNA to the cells is a promising approach. In order to introduce an antigen, a carrier for mRNA transfection is required, since the mRNA molecule per se is unstable in serum-containing medium. We previously reported on an ionizable lipid-like material with vitamin E-scaffolds (ssPalmE) as a material for a lipid nanoparticle (LNP)-based carrier for nucleic acids. In the present study, we report on the development of a lipoplex-type mRNA carrier for use as a DC-vaccine by using a combination of an ssPalmE-LNP and an α-helical cationic peptide "KALA" (ssPalmE-KALA). The transfection of mRNAs complexed with the ssPalmE-KALA achieved a significantly higher protein expression and the production of proinflammatory cytokines from murine bone marrow derived DCs (BMDCs) in comparison with a lipoplex that was prepared with an ssPalm with fatty acid-scaffolds (myristic acid; ssPalmM-KALA). A cellular uptake process and a pH-responsive membrane-destabilization activity cannot explain the preferred protein expression and immune-stimulation caused by the ssPalmE-KALA. Proteomic analyses suggest that transfection with the ssPalmM-KALA stimulates a down-regulatory pathway of translation, while the transfection with the ssPalmE-KALA does not stimulate it. In the vaccination with the BMDCs that were preliminarily transfected with an ovalbumin (OVA)-encoding mRNA elicited the induction OVA specific cytotoxic T-lymphocyte activity in vivo. In parallel, the vaccination induced significant prophylactic anti-tumor effects against a model tumor that stably expressed the OVA protein. Based on the above findings, the ssPalmE-KALA appears to be a potent ex vivo DCs-based RNA vaccine platform.
    MeSH term(s) Animals ; Cancer Vaccines/administration & dosage ; Cancer Vaccines/genetics ; Cancer Vaccines/immunology ; Cell-Penetrating Peptides/chemistry ; Cytokines/biosynthesis ; Dendritic Cells/immunology ; Drug Carriers/chemistry ; Gene Expression ; Lipids/chemistry ; Liposomes ; Mice, Inbred C57BL ; Ovalbumin/genetics ; Ovalbumin/immunology ; RNA, Messenger/administration & dosage ; RNA, Messenger/genetics ; RNA, Messenger/immunology ; T-Lymphocytes, Cytotoxic/immunology ; Vitamin E/chemistry
    Chemical Substances Cancer Vaccines ; Cell-Penetrating Peptides ; Cytokines ; Drug Carriers ; Lipids ; Liposomes ; RNA, Messenger ; Vitamin E (1406-18-4) ; Ovalbumin (9006-59-1)
    Language English
    Publishing date 2019-08-03
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2019.08.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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