AU2018269742B2 - Nano-enabled immunotherapy in cancer - Google Patents
Nano-enabled immunotherapy in cancer Download PDFInfo
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- AU2018269742B2 AU2018269742B2 AU2018269742A AU2018269742A AU2018269742B2 AU 2018269742 B2 AU2018269742 B2 AU 2018269742B2 AU 2018269742 A AU2018269742 A AU 2018269742A AU 2018269742 A AU2018269742 A AU 2018269742A AU 2018269742 B2 AU2018269742 B2 AU 2018269742B2
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Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201762507996P | 2017-05-18 | 2017-05-18 | |
US62/507,996 | 2017-05-18 | ||
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Families Citing this family (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107073090A (zh) | 2014-04-30 | 2017-08-18 | 哈佛学院董事会 | 结合的疫苗装置和杀死癌细胞的方法 |
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MA45738A (fr) | 2016-07-13 | 2019-05-22 | Harvard College | Échafaudages mimétiques de cellules présentant l'antigène et procédés pour les préparer et les utiliser |
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US20220226311A1 (en) * | 2019-05-30 | 2022-07-21 | The Board Of Trustees Of The University Of Illinois | Procaspase-3 activation and immunotherapy for treatment of cancer |
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WO2023172347A1 (en) | 2022-03-10 | 2023-09-14 | Nammi Therapeutics, Inc. | Formulated and/or co-formulated lipid nanocarriers compositions containing toll-like receptor ("tlr") agonist prodrugs useful in the treatment of cancer and methods thereof |
WO2023172300A1 (en) * | 2022-03-10 | 2023-09-14 | The Regents Of The University Of California | A drug nanocarrier system to deliver a combination of tlr agonists and/or a lipoxin plus immunogenic cell death inducing chemotherapeutic agents for cancer immunotherapy |
WO2023183872A1 (en) * | 2022-03-23 | 2023-09-28 | You First Services, Inc. | Delmopinol and delmopinol salt containing nanoparticles and uses thereof |
CN114748414B (zh) * | 2022-04-20 | 2024-05-31 | 中国医学科学院生物医学工程研究所 | 一种共负载化疗药和纳米粒的海藻酸钠水凝胶复合体系及其制备方法和应用 |
CN116327979B (zh) * | 2023-05-25 | 2023-08-01 | 西南石油大学 | 一种过渡金属基介孔纳米催化药物、制备方法及用途 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110159017A1 (en) * | 2008-04-11 | 2011-06-30 | Ludwig Institute For Cancer Research Ltd. | Trytophan catabolism in cancer treatment and diagnosis |
WO2017023667A1 (en) * | 2015-07-31 | 2017-02-09 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Immunostimulatory nanocarrier |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10828255B2 (en) * | 2013-03-05 | 2020-11-10 | The Regents Of The University Of California | Lipid bilayer coated mesoporous silica nanoparticles with a high loading capacity for one or more anticancer agents |
CN109310702A (zh) * | 2016-05-20 | 2019-02-05 | 芝加哥大学 | 用于化学疗法、靶向疗法、光动力疗法、免疫疗法和它们的任何组合的纳米颗粒 |
CA3051136A1 (en) * | 2017-01-27 | 2018-08-02 | The Methodist Hospital | Core/shell structure platform for immunotherapy |
WO2019173391A1 (en) * | 2018-03-06 | 2019-09-12 | Rita Elena Serda | A high capacity platform for immunogenic cancer cell death |
-
2018
- 2018-05-17 EP EP18803111.6A patent/EP3624810A4/de active Pending
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- 2018-05-17 AU AU2018269742A patent/AU2018269742B2/en active Active
- 2018-05-17 CA CA3063932A patent/CA3063932A1/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110159017A1 (en) * | 2008-04-11 | 2011-06-30 | Ludwig Institute For Cancer Research Ltd. | Trytophan catabolism in cancer treatment and diagnosis |
WO2017023667A1 (en) * | 2015-07-31 | 2017-02-09 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Immunostimulatory nanocarrier |
Non-Patent Citations (2)
Title |
---|
PURI A, ET AL., 'Lipid-Based Nanoparticles as Pharmaceutical Drug Carriers: From Concepts to Clinic', Critical Review Therapeutic Drug Carrier Systems, 2009, 26(6), pg 523-80. doi: 10.1615/critrevtherdrugcarriersyst.v26.i6.10. * |
SUN JJ ET AL., 'Programmable co-delivery of the immune checkpoint inhibitor NLG919 and chemotherapeutic doxorubicin via a redox-responsive immunostimulatory polymeric prodrug carrier' * |
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CA3063932A1 (en) | 2018-11-12 |
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AU2018269742A1 (en) | 2019-12-05 |
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