Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy
Natural killer (NK) cells are potential effector cells in cell-based cancer immunotherapy, particularly in the control of hematological malignancies. The chimeric antigen receptor (CAR) is an artificially modified fusion protein that consists of an extracellular antigen recognition domain fused to a...
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| Veröffentlicht in: | Acta pharmacologica Sinica 2018-02, Vol.39 (2), p.167-176 |
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| description | Natural killer (NK) cells are potential effector cells in cell-based cancer immunotherapy, particularly in the control of hematological malignancies. The chimeric antigen receptor (CAR) is an artificially modified fusion protein that consists of an extracellular antigen recognition domain fused to an intracellular signaling domain. T cells genetically modified with a CAR have demonstrated remarkable success in the treatment of hematological cancers. Compared to T cells, CAR-transduced NK cells (CAR-NK) exhibit several advantages, such as safety in clinical use, the mechanisms by which they recognize cancer cells, and their abundance in clinical samples. Human primary NK cells and the NK-92 cell line have been successfully transduced to express CARs against both hematological cancers and solid tumors in pre-clinical and clinical trials. However, many challenges and obstacles remain, such as the
ex vivo
expansion of CAR-modified primary NK cells and the low transduction efficiency of NK cells. Many strategies and technologies have been developed to improve the safety and therapeutic efficacy in CAR-based immunotherapy. Moreover, NK cells express a variety of activating receptors (NKRs), such as CD16, NKG2D, CD226 and NKp30, which might specifically recognize the ligands expressed on tumor cells. Based on the principle of NKR recognition, a strategy that targets NKRs is rapidly emerging. Given the promising clinical progress described in this review, CAR- and NKR-NK cell-based immunotherapy are likely promising new strategies for cancer therapy. |
| doi_str_mv | 10.1038/aps.2017.125 |
| format | Article |
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ex vivo
expansion of CAR-modified primary NK cells and the low transduction efficiency of NK cells. Many strategies and technologies have been developed to improve the safety and therapeutic efficacy in CAR-based immunotherapy. Moreover, NK cells express a variety of activating receptors (NKRs), such as CD16, NKG2D, CD226 and NKp30, which might specifically recognize the ligands expressed on tumor cells. Based on the principle of NKR recognition, a strategy that targets NKRs is rapidly emerging. Given the promising clinical progress described in this review, CAR- and NKR-NK cell-based immunotherapy are likely promising new strategies for cancer therapy.</description><identifier>ISSN: 1671-4083</identifier><identifier>EISSN: 1745-7254</identifier><identifier>DOI: 10.1038/aps.2017.125</identifier><identifier>PMID: 28880014</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Antigens ; Biomedical and Life Sciences ; Biomedicine ; Blood cancer ; Cancer ; Cancer immunotherapy ; CD16 antigen ; Cell Line, Tumor ; Chimeric antigen receptors ; Clinical trials ; Effector cells ; Fusion protein ; Genetic modification ; Genetic Vectors ; Hematology ; Humans ; Immunology ; Immunotherapy ; Immunotherapy - methods ; Internal Medicine ; Intracellular signalling ; Killer Cells, Natural - immunology ; Killer Cells, Natural - transplantation ; Lymphocytes ; Lymphocytes T ; Medical Microbiology ; Natural killer cells ; Neoplasms - therapy ; NKG2 antigen ; Pharmacology/Toxicology ; Receptors, Antigen - genetics ; Receptors, Antigen - immunology ; Review ; Signal transduction ; Solid tumors ; T cell receptors ; Tumor cells ; Tumors ; Vaccine ; Xenograft Model Antitumor Assays</subject><ispartof>Acta pharmacologica Sinica, 2018-02, Vol.39 (2), p.167-176</ispartof><rights>CPS and SIMM 2018</rights><rights>Copyright Nature Publishing Group Feb 2018</rights><rights>Copyright © 2018 CPS and SIMM 2018 CPS and SIMM</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c516t-52056fdcaac7d587cba4450d1ac4959a21deb228fd6af4a9517e3cec9bdf2c963</citedby><cites>FETCH-LOGICAL-c516t-52056fdcaac7d587cba4450d1ac4959a21deb228fd6af4a9517e3cec9bdf2c963</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800464/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800464/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28880014$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hu, Yuan</creatorcontrib><creatorcontrib>Tian, Zhi-gang</creatorcontrib><creatorcontrib>Zhang, Cai</creatorcontrib><title>Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy</title><title>Acta pharmacologica Sinica</title><addtitle>Acta Pharmacol Sin</addtitle><addtitle>Acta Pharmacol Sin</addtitle><description>Natural killer (NK) cells are potential effector cells in cell-based cancer immunotherapy, particularly in the control of hematological malignancies. The chimeric antigen receptor (CAR) is an artificially modified fusion protein that consists of an extracellular antigen recognition domain fused to an intracellular signaling domain. T cells genetically modified with a CAR have demonstrated remarkable success in the treatment of hematological cancers. Compared to T cells, CAR-transduced NK cells (CAR-NK) exhibit several advantages, such as safety in clinical use, the mechanisms by which they recognize cancer cells, and their abundance in clinical samples. Human primary NK cells and the NK-92 cell line have been successfully transduced to express CARs against both hematological cancers and solid tumors in pre-clinical and clinical trials. However, many challenges and obstacles remain, such as the
ex vivo
expansion of CAR-modified primary NK cells and the low transduction efficiency of NK cells. Many strategies and technologies have been developed to improve the safety and therapeutic efficacy in CAR-based immunotherapy. Moreover, NK cells express a variety of activating receptors (NKRs), such as CD16, NKG2D, CD226 and NKp30, which might specifically recognize the ligands expressed on tumor cells. Based on the principle of NKR recognition, a strategy that targets NKRs is rapidly emerging. Given the promising clinical progress described in this review, CAR- and NKR-NK cell-based immunotherapy are likely promising new strategies for cancer therapy.</description><subject>Animals</subject><subject>Antigens</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blood cancer</subject><subject>Cancer</subject><subject>Cancer immunotherapy</subject><subject>CD16 antigen</subject><subject>Cell Line, Tumor</subject><subject>Chimeric antigen receptors</subject><subject>Clinical trials</subject><subject>Effector cells</subject><subject>Fusion protein</subject><subject>Genetic modification</subject><subject>Genetic Vectors</subject><subject>Hematology</subject><subject>Humans</subject><subject>Immunology</subject><subject>Immunotherapy</subject><subject>Immunotherapy - methods</subject><subject>Internal Medicine</subject><subject>Intracellular signalling</subject><subject>Killer Cells, Natural - immunology</subject><subject>Killer Cells, Natural - transplantation</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Medical Microbiology</subject><subject>Natural killer cells</subject><subject>Neoplasms - therapy</subject><subject>NKG2 antigen</subject><subject>Pharmacology/Toxicology</subject><subject>Receptors, Antigen - genetics</subject><subject>Receptors, Antigen - immunology</subject><subject>Review</subject><subject>Signal transduction</subject><subject>Solid tumors</subject><subject>T cell receptors</subject><subject>Tumor cells</subject><subject>Tumors</subject><subject>Vaccine</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1671-4083</issn><issn>1745-7254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkU1r3DAURUVoyFe7yzoYukmhnkqyJFubQhiaJhAohKRb8UZ6nlFqy65kF_Lvq2GSkJQuhATvcPUuh5BTRheMVs0XGNOCU1YvGJd75IjVQpY1l-JdfqualYI21SE5TumB0opXTB-QQ940DaVMHJGfy43vMXpbQJj8GkMR0eI4DbE4X17cfiqnCCG52aIrAkxzhK745bsOY2Gx61LhQzHNfcZ9389hmDYYYXx8T_Zb6BJ-eLpPyP3lt7vlVXnz4_v18uKmtJKpqZScStU6C2BrJ5varkAISR0DK7TUwJnDFedN6xS0ArRkNVYWrV65llutqhPydZc7zqsencWQ9-3MGH0P8dEM4M3bSfAbsx7-GJn7CyVywPlTQBx-z5gm0_u0bQYBhzkZpiuleD46ox__QR-GOYZcL1Oa60ZSVWfq846ycUgpYvuyDKNmK8xkYWYrzGRhGT97XeAFfjaUgXIHpDwKa4yvfv1f4F8WHKIw</recordid><startdate>20180201</startdate><enddate>20180201</enddate><creator>Hu, Yuan</creator><creator>Tian, Zhi-gang</creator><creator>Zhang, Cai</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20180201</creationdate><title>Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy</title><author>Hu, Yuan ; Tian, Zhi-gang ; Zhang, Cai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c516t-52056fdcaac7d587cba4450d1ac4959a21deb228fd6af4a9517e3cec9bdf2c963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Antigens</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Blood cancer</topic><topic>Cancer</topic><topic>Cancer immunotherapy</topic><topic>CD16 antigen</topic><topic>Cell Line, Tumor</topic><topic>Chimeric antigen receptors</topic><topic>Clinical trials</topic><topic>Effector cells</topic><topic>Fusion protein</topic><topic>Genetic modification</topic><topic>Genetic Vectors</topic><topic>Hematology</topic><topic>Humans</topic><topic>Immunology</topic><topic>Immunotherapy</topic><topic>Immunotherapy - methods</topic><topic>Internal Medicine</topic><topic>Intracellular signalling</topic><topic>Killer Cells, Natural - immunology</topic><topic>Killer Cells, Natural - transplantation</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Medical Microbiology</topic><topic>Natural killer cells</topic><topic>Neoplasms - therapy</topic><topic>NKG2 antigen</topic><topic>Pharmacology/Toxicology</topic><topic>Receptors, Antigen - genetics</topic><topic>Receptors, Antigen - immunology</topic><topic>Review</topic><topic>Signal transduction</topic><topic>Solid tumors</topic><topic>T cell receptors</topic><topic>Tumor cells</topic><topic>Tumors</topic><topic>Vaccine</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hu, Yuan</creatorcontrib><creatorcontrib>Tian, Zhi-gang</creatorcontrib><creatorcontrib>Zhang, Cai</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Acta pharmacologica Sinica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hu, Yuan</au><au>Tian, Zhi-gang</au><au>Zhang, Cai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy</atitle><jtitle>Acta pharmacologica Sinica</jtitle><stitle>Acta Pharmacol Sin</stitle><addtitle>Acta Pharmacol Sin</addtitle><date>2018-02-01</date><risdate>2018</risdate><volume>39</volume><issue>2</issue><spage>167</spage><epage>176</epage><pages>167-176</pages><issn>1671-4083</issn><eissn>1745-7254</eissn><abstract>Natural killer (NK) cells are potential effector cells in cell-based cancer immunotherapy, particularly in the control of hematological malignancies. The chimeric antigen receptor (CAR) is an artificially modified fusion protein that consists of an extracellular antigen recognition domain fused to an intracellular signaling domain. T cells genetically modified with a CAR have demonstrated remarkable success in the treatment of hematological cancers. Compared to T cells, CAR-transduced NK cells (CAR-NK) exhibit several advantages, such as safety in clinical use, the mechanisms by which they recognize cancer cells, and their abundance in clinical samples. Human primary NK cells and the NK-92 cell line have been successfully transduced to express CARs against both hematological cancers and solid tumors in pre-clinical and clinical trials. However, many challenges and obstacles remain, such as the
ex vivo
expansion of CAR-modified primary NK cells and the low transduction efficiency of NK cells. Many strategies and technologies have been developed to improve the safety and therapeutic efficacy in CAR-based immunotherapy. Moreover, NK cells express a variety of activating receptors (NKRs), such as CD16, NKG2D, CD226 and NKp30, which might specifically recognize the ligands expressed on tumor cells. Based on the principle of NKR recognition, a strategy that targets NKRs is rapidly emerging. Given the promising clinical progress described in this review, CAR- and NKR-NK cell-based immunotherapy are likely promising new strategies for cancer therapy.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28880014</pmid><doi>10.1038/aps.2017.125</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antigens Biomedical and Life Sciences Biomedicine Blood cancer Cancer Cancer immunotherapy CD16 antigen Cell Line, Tumor Chimeric antigen receptors Clinical trials Effector cells Fusion protein Genetic modification Genetic Vectors Hematology Humans Immunology Immunotherapy Immunotherapy - methods Internal Medicine Intracellular signalling Killer Cells, Natural - immunology Killer Cells, Natural - transplantation Lymphocytes Lymphocytes T Medical Microbiology Natural killer cells Neoplasms - therapy NKG2 antigen Pharmacology/Toxicology Receptors, Antigen - genetics Receptors, Antigen - immunology Review Signal transduction Solid tumors T cell receptors Tumor cells Tumors Vaccine Xenograft Model Antitumor Assays |
| title | Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy |
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