Intrapulmonary Delivery of CpG Microparticles Eliminates Lung Tumors
CpG oligonucleotides (ODN) stimulate the innate immune system by triggering cells that express TLR9. The resulting response promotes tumor regression, an effect optimized by delivery of CpG ODN to the tumor site. This work examines the effect of instilling CpG ODN adsorbed onto polyketal micropartic...
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| Veröffentlicht in: | Molecular cancer therapeutics 2015-10, Vol.14 (10), p.2198-2205 |
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| creator | Sato, Takashi Shimosato, Takeshi Ueda, Atsuhisa Ishigatsubo, Yoshiaki Klinman, Dennis M |
| description | CpG oligonucleotides (ODN) stimulate the innate immune system by triggering cells that express TLR9. The resulting response promotes tumor regression, an effect optimized by delivery of CpG ODN to the tumor site. This work examines the effect of instilling CpG ODN adsorbed onto polyketal microparticles (CpG-MP) into the lungs of mice with non-small cell lung cancer. Intrapulmonary delivery of CpG-MP improved ODN uptake and retention at the tumor site, thereby inducing a stronger Th1 response than systemically administered or unadsorbed CpG ODN. CpG-MP reversed the immunosuppression that characterized the tumor microenvironment by (i) decreasing the number of immunosuppressive Tregs and M2 macrophages while (ii) increasing the number of tumoricidal CD8(+) T cells and M1 macrophages. These effects promoted tumor regression and culminated in 82% permanent survival of mice with otherwise fatal Lewis lung cancer. |
| doi_str_mv | 10.1158/1535-7163.mct-15-0401 |
| format | Article |
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The resulting response promotes tumor regression, an effect optimized by delivery of CpG ODN to the tumor site. This work examines the effect of instilling CpG ODN adsorbed onto polyketal microparticles (CpG-MP) into the lungs of mice with non-small cell lung cancer. Intrapulmonary delivery of CpG-MP improved ODN uptake and retention at the tumor site, thereby inducing a stronger Th1 response than systemically administered or unadsorbed CpG ODN. CpG-MP reversed the immunosuppression that characterized the tumor microenvironment by (i) decreasing the number of immunosuppressive Tregs and M2 macrophages while (ii) increasing the number of tumoricidal CD8(+) T cells and M1 macrophages. 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The resulting response promotes tumor regression, an effect optimized by delivery of CpG ODN to the tumor site. This work examines the effect of instilling CpG ODN adsorbed onto polyketal microparticles (CpG-MP) into the lungs of mice with non-small cell lung cancer. Intrapulmonary delivery of CpG-MP improved ODN uptake and retention at the tumor site, thereby inducing a stronger Th1 response than systemically administered or unadsorbed CpG ODN. CpG-MP reversed the immunosuppression that characterized the tumor microenvironment by (i) decreasing the number of immunosuppressive Tregs and M2 macrophages while (ii) increasing the number of tumoricidal CD8(+) T cells and M1 macrophages. 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Shimosato, Takeshi ; Ueda, Atsuhisa ; Ishigatsubo, Yoshiaki ; Klinman, Dennis M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-7833e37b7718cfc880186c9254e5f18358aa82bec872b32e84580279f9d03c323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Administration, Inhalation</topic><topic>Animals</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Capsules</topic><topic>Carcinoma, Lewis Lung - drug therapy</topic><topic>Carcinoma, Lewis Lung - immunology</topic><topic>Carcinoma, Lewis Lung - pathology</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Carcinoma, Non-Small-Cell Lung - immunology</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Immunity, Innate - drug effects</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - immunology</topic><topic>Lung Neoplasms - pathology</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Oligodeoxyribonucleotides - administration & dosage</topic><topic>Oligodeoxyribonucleotides - pharmacokinetics</topic><topic>Oligodeoxyribonucleotides - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sato, Takashi</creatorcontrib><creatorcontrib>Shimosato, Takeshi</creatorcontrib><creatorcontrib>Ueda, Atsuhisa</creatorcontrib><creatorcontrib>Ishigatsubo, Yoshiaki</creatorcontrib><creatorcontrib>Klinman, Dennis M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular cancer therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sato, Takashi</au><au>Shimosato, Takeshi</au><au>Ueda, Atsuhisa</au><au>Ishigatsubo, Yoshiaki</au><au>Klinman, Dennis M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intrapulmonary Delivery of CpG Microparticles Eliminates Lung Tumors</atitle><jtitle>Molecular cancer therapeutics</jtitle><addtitle>Mol Cancer Ther</addtitle><date>2015-10-01</date><risdate>2015</risdate><volume>14</volume><issue>10</issue><spage>2198</spage><epage>2205</epage><pages>2198-2205</pages><issn>1535-7163</issn><eissn>1538-8514</eissn><abstract>CpG oligonucleotides (ODN) stimulate the innate immune system by triggering cells that express TLR9. 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| source | MEDLINE; American Association for Cancer Research Journals; EZB* |
| subjects | Administration, Inhalation Animals Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacokinetics Antineoplastic Agents - pharmacology Capsules Carcinoma, Lewis Lung - drug therapy Carcinoma, Lewis Lung - immunology Carcinoma, Lewis Lung - pathology Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - immunology Carcinoma, Non-Small-Cell Lung - pathology Drug Screening Assays, Antitumor Immunity, Innate - drug effects Lung Neoplasms - drug therapy Lung Neoplasms - immunology Lung Neoplasms - pathology Mice, Inbred C57BL Mice, Knockout Oligodeoxyribonucleotides - administration & dosage Oligodeoxyribonucleotides - pharmacokinetics Oligodeoxyribonucleotides - pharmacology |
| title | Intrapulmonary Delivery of CpG Microparticles Eliminates Lung Tumors |
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