Cellular vesicles expressing PD-1-blocking scFv reinvigorate T cell immunity against cancer
Cancer cells aberrantly express immunosuppressive checkpoint ligands and produce certain metabolites that lead to T cell exhaustion. Immune checkpoint blockade (ICB) therapy that reinvigorates exhausted T cells have achieved impressive response in clinical cancer treatment. However, the limited clin...
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| Veröffentlicht in: | Nano research 2022-06, Vol.15 (6), p.5295-5304 |
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| container_title | Nano research |
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| creator | Xue, Tianyuan Zhang, Zhirang Fang, Tianliang Li, Baoqi Li, Yuan Li, Liyan Jiang, Yanghua Duan, Fangfang Meng, Fanqiang Liang, Xin Zhang, Xudong |
| description | Cancer cells aberrantly express immunosuppressive checkpoint ligands and produce certain metabolites that lead to T cell exhaustion. Immune checkpoint blockade (ICB) therapy that reinvigorates exhausted T cells have achieved impressive response in clinical cancer treatment. However, the limited clinical response rate and off-tumor toxicities restrict ICB therapy. Herein, cellular vesicles displaying anti-programmed cell death-1 (PD-1) single-chain variable fragment antibody (aPD-1-scFv) were prepared to reinvigorate T cell immunity to counteract cancer. The nanovesicles displaying aPD-1-scFv (aPD-1-scFv NVs) could enhance the anti-tumor activation of T cells through PD-1 blockade. Furthermore, NVs loading the A
2a
adenosine receptor (A
2a
R) antagonist CPI-444 assisted T cells to antagonize adenosine, an immunosuppressive metabolite produced by cancer cells. Hence, CPI-444 loaded aPD-1-scFv NVs could intensively increase the density and activity of tumor infiltrating T cells, directly restraining tumor progress and metastasis. |
| doi_str_mv | 10.1007/s12274-022-4182-0 |
| format | Article |
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2a
adenosine receptor (A
2a
R) antagonist CPI-444 assisted T cells to antagonize adenosine, an immunosuppressive metabolite produced by cancer cells. Hence, CPI-444 loaded aPD-1-scFv NVs could intensively increase the density and activity of tumor infiltrating T cells, directly restraining tumor progress and metastasis.</description><identifier>ISSN: 1998-0124</identifier><identifier>EISSN: 1998-0000</identifier><identifier>DOI: 10.1007/s12274-022-4182-0</identifier><language>eng</language><publisher>Beijing: Tsinghua University Press</publisher><subject>Adenosine ; Antibodies ; Apoptosis ; Atomic/Molecular Structure and Spectra ; Biomedicine ; Biotechnology ; Cancer ; Cancer therapies ; Cell activation ; Cell death ; Chemistry and Materials Science ; Condensed Matter Physics ; Immune checkpoint ; Immunity ; Immunotherapy ; Ligands ; Lymphocytes ; Lymphocytes T ; Materials Science ; Metabolites ; Metastases ; Nanoparticles ; Nanotechnology ; PD-1 protein ; Research Article ; Tumor-infiltrating lymphocytes ; Tumors ; Vesicles</subject><ispartof>Nano research, 2022-06, Vol.15 (6), p.5295-5304</ispartof><rights>Tsinghua University Press 2022</rights><rights>Tsinghua University Press 2022.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c316t-cfe97d47198ab0a0588e001ae6d6d5766ae9bcb73a9baa8e9caaf9aff279f7133</citedby><cites>FETCH-LOGICAL-c316t-cfe97d47198ab0a0588e001ae6d6d5766ae9bcb73a9baa8e9caaf9aff279f7133</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12274-022-4182-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12274-022-4182-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids></links><search><creatorcontrib>Xue, Tianyuan</creatorcontrib><creatorcontrib>Zhang, Zhirang</creatorcontrib><creatorcontrib>Fang, Tianliang</creatorcontrib><creatorcontrib>Li, Baoqi</creatorcontrib><creatorcontrib>Li, Yuan</creatorcontrib><creatorcontrib>Li, Liyan</creatorcontrib><creatorcontrib>Jiang, Yanghua</creatorcontrib><creatorcontrib>Duan, Fangfang</creatorcontrib><creatorcontrib>Meng, Fanqiang</creatorcontrib><creatorcontrib>Liang, Xin</creatorcontrib><creatorcontrib>Zhang, Xudong</creatorcontrib><title>Cellular vesicles expressing PD-1-blocking scFv reinvigorate T cell immunity against cancer</title><title>Nano research</title><addtitle>Nano Res</addtitle><description>Cancer cells aberrantly express immunosuppressive checkpoint ligands and produce certain metabolites that lead to T cell exhaustion. Immune checkpoint blockade (ICB) therapy that reinvigorates exhausted T cells have achieved impressive response in clinical cancer treatment. However, the limited clinical response rate and off-tumor toxicities restrict ICB therapy. Herein, cellular vesicles displaying anti-programmed cell death-1 (PD-1) single-chain variable fragment antibody (aPD-1-scFv) were prepared to reinvigorate T cell immunity to counteract cancer. The nanovesicles displaying aPD-1-scFv (aPD-1-scFv NVs) could enhance the anti-tumor activation of T cells through PD-1 blockade. Furthermore, NVs loading the A
2a
adenosine receptor (A
2a
R) antagonist CPI-444 assisted T cells to antagonize adenosine, an immunosuppressive metabolite produced by cancer cells. Hence, CPI-444 loaded aPD-1-scFv NVs could intensively increase the density and activity of tumor infiltrating T cells, directly restraining tumor progress and metastasis.</description><subject>Adenosine</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Atomic/Molecular Structure and Spectra</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cell activation</subject><subject>Cell death</subject><subject>Chemistry and Materials Science</subject><subject>Condensed Matter Physics</subject><subject>Immune checkpoint</subject><subject>Immunity</subject><subject>Immunotherapy</subject><subject>Ligands</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Materials Science</subject><subject>Metabolites</subject><subject>Metastases</subject><subject>Nanoparticles</subject><subject>Nanotechnology</subject><subject>PD-1 protein</subject><subject>Research Article</subject><subject>Tumor-infiltrating lymphocytes</subject><subject>Tumors</subject><subject>Vesicles</subject><issn>1998-0124</issn><issn>1998-0000</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kE1PwzAMhiMEEmPwA7hF4hxI0i4fRzQYICHBYZw4RG7mVhldO5J2Yv-eTgVxwhfb0vvY0kPIpeDXgnN9k4SUOmdcSpYLIxk_IhNhrWF8qOPfWcj8lJyltOZcSZGbCXmfY133NUS6wxR8jYni1zZiSqGp6OsdE6yoW_9x2JJf7GjE0OxC1UbokC6pH3AaNpu-Cd2eQgWhSR310HiM5-SkhDrhxU-fkrfF_XL-yJ5fHp7mt8_MZ0J1zJdo9SrXwhooOPCZMci5AFQrtZpppQBt4QudgS0ADFoPUFooS6ltqUWWTcnVeHcb288eU-fWbR-b4aWTSmcyz4yRQ0qMKR_blCKWbhvDBuLeCe4ODt3o0A0O3cGh4wMjRyYN2abC-Hf5f-gbUYR1Yg</recordid><startdate>20220601</startdate><enddate>20220601</enddate><creator>Xue, Tianyuan</creator><creator>Zhang, 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B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SE</scope><scope>7SR</scope><scope>7U5</scope><scope>7X7</scope><scope>7XB</scope><scope>8AO</scope><scope>8BQ</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H8G</scope><scope>HCIFZ</scope><scope>JG9</scope><scope>K9.</scope><scope>KB.</scope><scope>L7M</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>P64</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope></search><sort><creationdate>20220601</creationdate><title>Cellular vesicles expressing PD-1-blocking scFv reinvigorate T cell immunity against cancer</title><author>Xue, Tianyuan ; Zhang, Zhirang ; Fang, Tianliang ; Li, Baoqi ; Li, Yuan ; Li, Liyan ; Jiang, Yanghua ; Duan, Fangfang ; Meng, Fanqiang ; Liang, Xin ; Zhang, Xudong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c316t-cfe97d47198ab0a0588e001ae6d6d5766ae9bcb73a9baa8e9caaf9aff279f7133</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adenosine</topic><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Atomic/Molecular Structure and Spectra</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Cell activation</topic><topic>Cell death</topic><topic>Chemistry and Materials Science</topic><topic>Condensed Matter Physics</topic><topic>Immune checkpoint</topic><topic>Immunity</topic><topic>Immunotherapy</topic><topic>Ligands</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Materials Science</topic><topic>Metabolites</topic><topic>Metastases</topic><topic>Nanoparticles</topic><topic>Nanotechnology</topic><topic>PD-1 protein</topic><topic>Research Article</topic><topic>Tumor-infiltrating lymphocytes</topic><topic>Tumors</topic><topic>Vesicles</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xue, Tianyuan</creatorcontrib><creatorcontrib>Zhang, Zhirang</creatorcontrib><creatorcontrib>Fang, Tianliang</creatorcontrib><creatorcontrib>Li, Baoqi</creatorcontrib><creatorcontrib>Li, Yuan</creatorcontrib><creatorcontrib>Li, Liyan</creatorcontrib><creatorcontrib>Jiang, Yanghua</creatorcontrib><creatorcontrib>Duan, Fangfang</creatorcontrib><creatorcontrib>Meng, Fanqiang</creatorcontrib><creatorcontrib>Liang, Xin</creatorcontrib><creatorcontrib>Zhang, 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Yanghua</au><au>Duan, Fangfang</au><au>Meng, Fanqiang</au><au>Liang, Xin</au><au>Zhang, Xudong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cellular vesicles expressing PD-1-blocking scFv reinvigorate T cell immunity against cancer</atitle><jtitle>Nano research</jtitle><stitle>Nano Res</stitle><date>2022-06-01</date><risdate>2022</risdate><volume>15</volume><issue>6</issue><spage>5295</spage><epage>5304</epage><pages>5295-5304</pages><issn>1998-0124</issn><eissn>1998-0000</eissn><abstract>Cancer cells aberrantly express immunosuppressive checkpoint ligands and produce certain metabolites that lead to T cell exhaustion. Immune checkpoint blockade (ICB) therapy that reinvigorates exhausted T cells have achieved impressive response in clinical cancer treatment. However, the limited clinical response rate and off-tumor toxicities restrict ICB therapy. Herein, cellular vesicles displaying anti-programmed cell death-1 (PD-1) single-chain variable fragment antibody (aPD-1-scFv) were prepared to reinvigorate T cell immunity to counteract cancer. The nanovesicles displaying aPD-1-scFv (aPD-1-scFv NVs) could enhance the anti-tumor activation of T cells through PD-1 blockade. Furthermore, NVs loading the A
2a
adenosine receptor (A
2a
R) antagonist CPI-444 assisted T cells to antagonize adenosine, an immunosuppressive metabolite produced by cancer cells. Hence, CPI-444 loaded aPD-1-scFv NVs could intensively increase the density and activity of tumor infiltrating T cells, directly restraining tumor progress and metastasis.</abstract><cop>Beijing</cop><pub>Tsinghua University Press</pub><doi>10.1007/s12274-022-4182-0</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1998-0124 |
| ispartof | Nano research, 2022-06, Vol.15 (6), p.5295-5304 |
| issn | 1998-0124 1998-0000 |
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| source | SpringerNature Journals |
| subjects | Adenosine Antibodies Apoptosis Atomic/Molecular Structure and Spectra Biomedicine Biotechnology Cancer Cancer therapies Cell activation Cell death Chemistry and Materials Science Condensed Matter Physics Immune checkpoint Immunity Immunotherapy Ligands Lymphocytes Lymphocytes T Materials Science Metabolites Metastases Nanoparticles Nanotechnology PD-1 protein Research Article Tumor-infiltrating lymphocytes Tumors Vesicles |
| title | Cellular vesicles expressing PD-1-blocking scFv reinvigorate T cell immunity against cancer |
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