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Photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes to promote PD-L1 multivalent binding for effective immune checkpoint blockade therapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1428-1440页

作者： Youngjoo Lee Sukyung Song Suah Yang Jinseong Kim Yujeong Moon nayeon shim Hong Yeol Yoon Sehoon Kim Man Kyu shim Kwangmeyung Kim KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul 02841Republic of Korea Medicinal Materials Research Center Biomedical Research DivisionKorea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea College of Pharmacy Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoul 03760Republic of Korea Department of Bioengineering Korea UniversitySeoul 02841Republic of Korea

Immune checkpoint blockade(ICB)therapy targeting PD-L1 via monoclonal antibody(m Ab)has shown extensive clinical benefits in the diverse types of advanced ***,most patients are completely refractory to ICB therapy owing to the PD-L1 recycling ***,we propose photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes(immune checkpoint blockade liposomes;ICB-LPs)to promote PD-L1 multivalent binding for inducing lysosomal degradation of PD-L1 in tumor *** ICB-LPs are prepared by formulation of DC_(8,9)PC with photo-polymerized diacetylenic moiety,1,2-dipalmitoylphosphatidylcholine(DPPC)and anti-PD-L1peptide(D-form NYSKPTDRQYHF)-conjugated DSPE-PEG_(2k)(anti-PD-L1-DSPE-PEG_(2k))in a molar ratio of 45:45:10,followed by cross-linking of liposomal bilayer upon UV *** 10 mol% antiPD-L1-DSPE-PEG_(2k)incorporated ICB-LPs have a nano-sized lipid bilayer structure with an average diameter of 137.7±1.04 nm,showing a high stability in serum ***,the ICB-LPs efficiently promote the multivalent binding with PD-L1 on the tumor cell membrane,which are endocytosed with aim to deliver PD-L1 to the lysosomes,wherein the durable PD-L1 degradation is observed for72 h,in contrast to anti PD-L1 m Abs showing the rapid PD-L1 recycling within 9 *** in vitro coculture experiments with CD8^(+)T cells show that ICB-LPs effectively enhance the T cell-mediated antitumor immune responses against tumor cells by blocking the PD-L1/PD-1 *** ICB-LPs are intravenously injected into colon tumor-bearing mice,they efficiently accumulate within the targeted tumor tissues via both passive and active tumor targeting,inducing a potent T cell-mediated antitumor immune response by effective and durable PD-L1 ***,this study demonstrates the superior antitumor efficacy of crosslinked and anti-PD-L1 peptide incorporated liposome formulation that promotes PD-L1 multivalent binding for trafficking of PD-L1 toward

关键词： Cancer immunotherapy Immune checkpoint blockade PEGylated liposome Crosslinked lipid nanoparticles Anti-PD-L1 peptide Tumor-targeting PD-L1 multivalent binding Lysosomal PD-L1 degradation

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FBX015 plays a critical suppressive functional role in regulation of breast cancer progression

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Signal Transduction and Targeted Therapy 2021年第7期6卷 1972-1975页

作者： Yi Zhao nayeon shim Yan-Hong Cui Jae-Hyeok Kang Ki-Chun Yoo Seungmo Kim Joo Mi Yi Min-Jung Kim Jai Hoon Yoon Su-Jae Lee Department of Life Science Research Institute for Natural SciencesHanyang UniversitySeoulSouth Korea Department of Medicine Section of DermatologyUniversity of ChicagoChicagoILUSA Department of Microbiology and Immunology College of MedicineInje UniversityBusanSouth Korea Laboratory of Radiation Exposure and Therapeutics National Radiation Emergency Medical CenterKorea Institute of Radiological and Medical SciencesSeoulSouth Korea Department of Internal Medicine College of MedicineHanyang UniversitySeoulSouth Korea

Dear Editor,Breast cancer is a leading type of cancer in women,the treatment of basal type,including triple negative breast cancer(TNBC),remains challenging due to its aggressive behaviors and lack of targeted therapeutic options1.F-box proteins(FBPs)can serve as either oncogenes or tumor suppressors depending on their substrates,and various studies have been conducted on their involvement in different types of cancer and play significant roles in cancer development and ***,the related mechanisms and targets of F-box protein 15(FBX015)are still remain unclear in human breast cancers.

关键词： breast involvement Breast

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