{"created":"2023-05-15T14:48:50.542896+00:00","id":66904,"links":{},"metadata":{"_buckets":{"deposit":"98837b3d-15a1-4720-ba4f-3e2acfc72ee7"},"_deposit":{"created_by":1,"id":"66904","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"66904"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00066904","sets":["10:29"]},"author_link":["657777","657779","657773","657775","657776","657774","657780","657778"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2018-09-08","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Background:\nProgrammed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are recognized as promising targets for cancer immunotherapy. Binding of PD-L1 to PD-1 determines a downregulation of T-cell effector functions in cancer patients, inhibiting the antitumor immune response and leading to T-cell exhaustion. Blockade of PD-1/PD-L1 can strengthen the function of effector T cells and increase their production of cytokines through reactivation. Current medication directed toward the PD-1/PD-L1 axis includes monoclonal antibodies. Although great progress has been made, therapeutic antibodies exhibit several disadvantages such as: (1) limited tissue and tumor penetration, (2) lacking oral bioavailability, (3) immunogenicity, and (4) difficult production and high cost. Moreover, current PD-1/PD-L1 axis directed monoclonal antibodies lead to a tumor response only in a small fraction of all known tumor types.    \nDesign and Methods:\nThe research of peptide modulator of PD-1/PD-L1 PPIs is significant for both imaging of PD-L1 of the tumor immune microenvironment and anti-cancer therapy. The main goal of this project is to develop radiolabeled PD-L1 peptide modulators with high binding affinity and high specificity. Moreover, as proof-of-concept, this project will demonstrate peptide for radiotherapy and imaging. The bacteria surface display screened a lead peptide TPP-1. Then molecular dynamics docking was performed. Based on the complex structure, the peptide was bound PD-L1 protein with β-hairpin conformation. We then labelled the peptide with 64Cu. The PET imaging of peptide in MDA-231 xenograft mice will be performed. The distribution in vivo will be quantitatively analyzed. After that, peptide cyclization strategies will be utilized to stabilize the peptide into β-hairpin conformation. \nResults:\n1. TPP-1 peptide binds to PD-L1 protein in β-hairpin Conformation.\n2. The C- terminal of the peptide is a well-defined β-hairpin structure, however, the N-terminal of the peptide is a random coil structure. \n3. The labelled peptide is very stable in saline, and its half-life in serum is about 6 hours. \n4. The labelled peptide was majorly metabolized by liver and kidney. It will be excreted by urethra.\n5. The labelled peptide has some specific accumulation in spleen in normal mice.   \nConclusion:\nTPP-1 peptide is a potential PET tracer for PD-L1 imaging and a lead compound for immune checkpoint therapy. Through peptide stapling technique to constrain the peptide into β-hairpin, this peptide is capable of oral administration for Immunol cancer therapy.","subitem_description_type":"Abstract"}]},"item_10005_description_6":{"attribute_name":"会議概要（会議名, 開催地, 会期, 主催者等）","attribute_value_mlt":[{"subitem_description":"第2回日本核医学会分科会 放射性薬品科学研究会 第18回放射性医薬品・画像診断薬研究会","subitem_description_type":"Other"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Kuan, Hu"}],"nameIdentifiers":[{"nameIdentifier":"657773","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"謝, 琳"}],"nameIdentifiers":[{"nameIdentifier":"657774","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"破入, 正行"}],"nameIdentifiers":[{"nameIdentifier":"657775","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"張, 明栄"}],"nameIdentifiers":[{"nameIdentifier":"657776","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hu Kuan","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"657777","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"謝 琳","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"657778","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"破入 正行","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"657779","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"張 明栄","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"657780","nameIdentifierScheme":"WEKO"}]}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"conference object","resourceuri":"http://purl.org/coar/resource_type/c_c94f"}]},"item_title":"PD-L1をターゲットするPET診断及びがん免疫治療用の新規標識ペプチドの開発研究","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"PD-L1をターゲットするPET診断及びがん免疫治療用の新規標識ペプチドの開発研究"}]},"item_type_id":"10005","owner":"1","path":["29"],"pubdate":{"attribute_name":"公開日","attribute_value":"2018-09-12"},"publish_date":"2018-09-12","publish_status":"0","recid":"66904","relation_version_is_last":true,"title":["PD-L1をターゲットするPET診断及びがん免疫治療用の新規標識ペプチドの開発研究"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-15T20:43:38.893208+00:00"}