Development of adoptive immunotherapy with KK‐LC‐1‐specific TCR‐transduced γδT cells against lung cancer cells
The present study analyzed the antitumor effect of γδT cells transduced with the TCR of cancer‐specific CTLs to establish forceful cancer‐specific adoptive immunotherapy. We cloned the TCRαβ genes from CTLs showing HLA‐B15 restricted recognition of Kita‐Kyushu lung cancer antigen‐1 (KK‐LC‐1), a canc...
Gespeichert in:
| Veröffentlicht in: | Cancer science 2020-11, Vol.111 (11), p.4021-4030 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 4030 |
|---|---|
| container_issue | 11 |
| container_start_page | 4021 |
| container_title | Cancer science |
| container_volume | 111 |
| creator | Ichiki, Yoshinobu Shigematsu, Yoshiki Baba, Tetsuro Shiota, Hironobu Fukuyama, Takashi Nagata, Yoshika So, Tetsuya Yasuda, Manabu Takenoyama, Mitsuhiro Yasumoto, Kosei |
| description | The present study analyzed the antitumor effect of γδT cells transduced with the TCR of cancer‐specific CTLs to establish forceful cancer‐specific adoptive immunotherapy. We cloned the TCRαβ genes from CTLs showing HLA‐B15 restricted recognition of Kita‐Kyushu lung cancer antigen‐1 (KK‐LC‐1), a cancer/germline gene antigen, identified in a lung adenocarcinoma case (F1121). The TCRαβ and CD8 genes were transduced into γδT cells induced from PBLs of healthy volunteers stimulated with zoledronate and IL‐2. The KK‐LC‐1‐specific TCRαβ‐CD8 γδT cells showed cytotoxic activity against the KK‐LC‐1 positive lung cancer cell line F1121L and produced IFN‐γ against F1121L and KK‐LC‐1 peptide‐pulsed F1121 EBV‐B cells. These responses were blocked by HLA class I and HLA‐B/C antibodies. An in vivo assay using NOD/SCID mice with xenotransplantation of human lung cancer cells was performed, and the TCRαβ‐CD8 transduced γδT cells (TCRαβ‐CD8 γδT cells) were intravenously injected. Growth inhibition of KK‐LC‐1+, HLA‐B15+ lung cancer cells was confirmed in mice with injection of the TCRαβ‐CD8 γδT cells from 1 wk after xenotransplantation of cancer cells but not in those treated 2 wk after xenotransplantation. The resected specimens of the tumor, 2 wk after xenotransplantation, highly expressed FasL but not programmed death ligand‐1 (PD‐L1) by immunohistochemical staining. FasL highly expressed cancer cells xenotransplanted 2 wk ago were resistant to TCRαβ‐CD8 γδT cells injection. These results suggested that apoptosis of Fas‐positive TCRαβ‐CD8 γδT cells may be induced by a Fas‐mediated signal after interacting with FasL‐positive cancer cells.
(1) Kita‐Kyushu lung cancer antigen‐1 (KK‐LC‐1)‐specific cytotoxicity, which is the same as that observed in CTL clones, was obtained by transducing KK‐LC‐1‐specific TCRαβ and CD8 cells into γδT cells. (2) An in vivo assay using NOD/SCID mice with xenotransplantation of human lung cancer cells was performed, and the TCRαβ‐CD8 transduced γδT cells were intravenously injected. Growth inhibition of KK‐LC‐1+, HLA‐B15+ lung cancer cells was observed in mice with tumors 1 wk after xenotransplantation but not in those mice with tumors 2 wk after xenotransplantation. (3) Cancer cells expressed a high level of FasL at 2 wk after xenotransplantation and escaped adoptive treatment. We should be alert for Fas‐mediated apoptosis when applying such cellular immunotherapy. |
| doi_str_mv | 10.1111/cas.14612 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7648040</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2458218092</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4672-6f3c852b27703e146847f2ffbe3a7e72527eb11cb04e38fa60d5eccc1aa240e13</originalsourceid><addsrcrecordid>eNp1kc1u1DAQxy1ERb848ALIEicOaf2VOHtBqlIKqCsh0eVsOc5411USBzvZsjcegXeB5-hD8CS4TanggKXxeDQ__T2jP0IvKDmh6ZwaHU-oKCh7gg4oF4tMElI8vX_LbEE420eHMV4TwguxEM_QPmeyJDkrD9DXc9hC64cO-hF7i3Xjh9FtAbuum3o_biDoYYdv3LjBl5e_vn1fVumiKeIAxlln8Kr6lMox6D42k4EG3_64_bnCBto2Yr3Wro8jbqd-jY3uDYS5c4z2rG4jPH_IR-jzxdtV9T5bfnz3oTpbZkYUkmWF5abMWc2kJBzSkqWQlllbA9cSJMuZhJpSUxMBvLS6IE0OxhiqNRMEKD9Cb2bdYao7aEzaM-hWDcF1OuyU10792-ndRq39VslClESQJPDqQSD4LxPEUV37KfRpZsVEXjJakgVL1OuZMsHHGMA-_kCJujNJJZPUvUmJffn3SI_kH1cScDoDN66F3f-VVHV2NUv-Bk1Qou8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2458218092</pqid></control><display><type>article</type><title>Development of adoptive immunotherapy with KK‐LC‐1‐specific TCR‐transduced γδT cells against lung cancer cells</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Access via Wiley Online Library</source><source>Wiley Online Library (Open Access Collection)</source><source>PubMed Central</source><creator>Ichiki, Yoshinobu ; Shigematsu, Yoshiki ; Baba, Tetsuro ; Shiota, Hironobu ; Fukuyama, Takashi ; Nagata, Yoshika ; So, Tetsuya ; Yasuda, Manabu ; Takenoyama, Mitsuhiro ; Yasumoto, Kosei</creator><creatorcontrib>Ichiki, Yoshinobu ; Shigematsu, Yoshiki ; Baba, Tetsuro ; Shiota, Hironobu ; Fukuyama, Takashi ; Nagata, Yoshika ; So, Tetsuya ; Yasuda, Manabu ; Takenoyama, Mitsuhiro ; Yasumoto, Kosei</creatorcontrib><description>The present study analyzed the antitumor effect of γδT cells transduced with the TCR of cancer‐specific CTLs to establish forceful cancer‐specific adoptive immunotherapy. We cloned the TCRαβ genes from CTLs showing HLA‐B15 restricted recognition of Kita‐Kyushu lung cancer antigen‐1 (KK‐LC‐1), a cancer/germline gene antigen, identified in a lung adenocarcinoma case (F1121). The TCRαβ and CD8 genes were transduced into γδT cells induced from PBLs of healthy volunteers stimulated with zoledronate and IL‐2. The KK‐LC‐1‐specific TCRαβ‐CD8 γδT cells showed cytotoxic activity against the KK‐LC‐1 positive lung cancer cell line F1121L and produced IFN‐γ against F1121L and KK‐LC‐1 peptide‐pulsed F1121 EBV‐B cells. These responses were blocked by HLA class I and HLA‐B/C antibodies. An in vivo assay using NOD/SCID mice with xenotransplantation of human lung cancer cells was performed, and the TCRαβ‐CD8 transduced γδT cells (TCRαβ‐CD8 γδT cells) were intravenously injected. Growth inhibition of KK‐LC‐1+, HLA‐B15+ lung cancer cells was confirmed in mice with injection of the TCRαβ‐CD8 γδT cells from 1 wk after xenotransplantation of cancer cells but not in those treated 2 wk after xenotransplantation. The resected specimens of the tumor, 2 wk after xenotransplantation, highly expressed FasL but not programmed death ligand‐1 (PD‐L1) by immunohistochemical staining. FasL highly expressed cancer cells xenotransplanted 2 wk ago were resistant to TCRαβ‐CD8 γδT cells injection. These results suggested that apoptosis of Fas‐positive TCRαβ‐CD8 γδT cells may be induced by a Fas‐mediated signal after interacting with FasL‐positive cancer cells.
(1) Kita‐Kyushu lung cancer antigen‐1 (KK‐LC‐1)‐specific cytotoxicity, which is the same as that observed in CTL clones, was obtained by transducing KK‐LC‐1‐specific TCRαβ and CD8 cells into γδT cells. (2) An in vivo assay using NOD/SCID mice with xenotransplantation of human lung cancer cells was performed, and the TCRαβ‐CD8 transduced γδT cells were intravenously injected. Growth inhibition of KK‐LC‐1+, HLA‐B15+ lung cancer cells was observed in mice with tumors 1 wk after xenotransplantation but not in those mice with tumors 2 wk after xenotransplantation. (3) Cancer cells expressed a high level of FasL at 2 wk after xenotransplantation and escaped adoptive treatment. We should be alert for Fas‐mediated apoptosis when applying such cellular immunotherapy.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.14612</identifier><identifier>PMID: 32780528</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Adenocarcinoma ; Adoptive immunotherapy ; Animals ; Antigens ; Antigens, Neoplasm - immunology ; Antitumor activity ; Apoptosis ; CD8 antigen ; Cell Line, Tumor ; Cervical cancer ; Cloning ; CTL ; Cytokines ; Cytokines - metabolism ; Cytotoxicity ; Disease Models, Animal ; FasL ; FasL protein ; Flow cytometry ; Genes ; Growth inhibition ; Histocompatibility antigen HLA ; Humans ; Immunomodulation ; Immunotherapy ; Immunotherapy, Adoptive ; Injection ; Interferon ; KK‐LC‐1 ; Laboratories ; Ligands ; Lung cancer ; Lung Neoplasms - etiology ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Lung Neoplasms - therapy ; Lymphatic system ; Lymphocytes ; Lymphocytes B ; Lymphocytes, Tumor-Infiltrating - immunology ; Lymphocytes, Tumor-Infiltrating - metabolism ; Lymphocytes, Tumor-Infiltrating - pathology ; Metastasis ; Mice, Transgenic ; Original ; Patients ; PD-L1 protein ; Peptides ; Receptors, Antigen, T-Cell, gamma-delta - metabolism ; T cell receptors ; T-Lymphocyte Subsets - immunology ; T-Lymphocyte Subsets - metabolism ; T-Lymphocytes, Cytotoxic - immunology ; T-Lymphocytes, Cytotoxic - metabolism ; Transduction, Genetic ; Treatment Outcome ; Tumor necrosis factor-TNF ; T‐cell receptor ; Xenograft Model Antitumor Assays ; Xenografts ; Zoledronic acid</subject><ispartof>Cancer science, 2020-11, Vol.111 (11), p.4021-4030</ispartof><rights>2020 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association</rights><rights>2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2020. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4672-6f3c852b27703e146847f2ffbe3a7e72527eb11cb04e38fa60d5eccc1aa240e13</citedby><cites>FETCH-LOGICAL-c4672-6f3c852b27703e146847f2ffbe3a7e72527eb11cb04e38fa60d5eccc1aa240e13</cites><orcidid>0000-0002-1293-6952</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648040/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648040/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1417,11562,27924,27925,45574,45575,46052,46476,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32780528$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ichiki, Yoshinobu</creatorcontrib><creatorcontrib>Shigematsu, Yoshiki</creatorcontrib><creatorcontrib>Baba, Tetsuro</creatorcontrib><creatorcontrib>Shiota, Hironobu</creatorcontrib><creatorcontrib>Fukuyama, Takashi</creatorcontrib><creatorcontrib>Nagata, Yoshika</creatorcontrib><creatorcontrib>So, Tetsuya</creatorcontrib><creatorcontrib>Yasuda, Manabu</creatorcontrib><creatorcontrib>Takenoyama, Mitsuhiro</creatorcontrib><creatorcontrib>Yasumoto, Kosei</creatorcontrib><title>Development of adoptive immunotherapy with KK‐LC‐1‐specific TCR‐transduced γδT cells against lung cancer cells</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>The present study analyzed the antitumor effect of γδT cells transduced with the TCR of cancer‐specific CTLs to establish forceful cancer‐specific adoptive immunotherapy. We cloned the TCRαβ genes from CTLs showing HLA‐B15 restricted recognition of Kita‐Kyushu lung cancer antigen‐1 (KK‐LC‐1), a cancer/germline gene antigen, identified in a lung adenocarcinoma case (F1121). The TCRαβ and CD8 genes were transduced into γδT cells induced from PBLs of healthy volunteers stimulated with zoledronate and IL‐2. The KK‐LC‐1‐specific TCRαβ‐CD8 γδT cells showed cytotoxic activity against the KK‐LC‐1 positive lung cancer cell line F1121L and produced IFN‐γ against F1121L and KK‐LC‐1 peptide‐pulsed F1121 EBV‐B cells. These responses were blocked by HLA class I and HLA‐B/C antibodies. An in vivo assay using NOD/SCID mice with xenotransplantation of human lung cancer cells was performed, and the TCRαβ‐CD8 transduced γδT cells (TCRαβ‐CD8 γδT cells) were intravenously injected. Growth inhibition of KK‐LC‐1+, HLA‐B15+ lung cancer cells was confirmed in mice with injection of the TCRαβ‐CD8 γδT cells from 1 wk after xenotransplantation of cancer cells but not in those treated 2 wk after xenotransplantation. The resected specimens of the tumor, 2 wk after xenotransplantation, highly expressed FasL but not programmed death ligand‐1 (PD‐L1) by immunohistochemical staining. FasL highly expressed cancer cells xenotransplanted 2 wk ago were resistant to TCRαβ‐CD8 γδT cells injection. These results suggested that apoptosis of Fas‐positive TCRαβ‐CD8 γδT cells may be induced by a Fas‐mediated signal after interacting with FasL‐positive cancer cells.
(1) Kita‐Kyushu lung cancer antigen‐1 (KK‐LC‐1)‐specific cytotoxicity, which is the same as that observed in CTL clones, was obtained by transducing KK‐LC‐1‐specific TCRαβ and CD8 cells into γδT cells. (2) An in vivo assay using NOD/SCID mice with xenotransplantation of human lung cancer cells was performed, and the TCRαβ‐CD8 transduced γδT cells were intravenously injected. Growth inhibition of KK‐LC‐1+, HLA‐B15+ lung cancer cells was observed in mice with tumors 1 wk after xenotransplantation but not in those mice with tumors 2 wk after xenotransplantation. (3) Cancer cells expressed a high level of FasL at 2 wk after xenotransplantation and escaped adoptive treatment. We should be alert for Fas‐mediated apoptosis when applying such cellular immunotherapy.</description><subject>Adenocarcinoma</subject><subject>Adoptive immunotherapy</subject><subject>Animals</subject><subject>Antigens</subject><subject>Antigens, Neoplasm - immunology</subject><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>CD8 antigen</subject><subject>Cell Line, Tumor</subject><subject>Cervical cancer</subject><subject>Cloning</subject><subject>CTL</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Cytotoxicity</subject><subject>Disease Models, Animal</subject><subject>FasL</subject><subject>FasL protein</subject><subject>Flow cytometry</subject><subject>Genes</subject><subject>Growth inhibition</subject><subject>Histocompatibility antigen HLA</subject><subject>Humans</subject><subject>Immunomodulation</subject><subject>Immunotherapy</subject><subject>Immunotherapy, Adoptive</subject><subject>Injection</subject><subject>Interferon</subject><subject>KK‐LC‐1</subject><subject>Laboratories</subject><subject>Ligands</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - etiology</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Lung Neoplasms - therapy</subject><subject>Lymphatic system</subject><subject>Lymphocytes</subject><subject>Lymphocytes B</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Lymphocytes, Tumor-Infiltrating - metabolism</subject><subject>Lymphocytes, Tumor-Infiltrating - pathology</subject><subject>Metastasis</subject><subject>Mice, Transgenic</subject><subject>Original</subject><subject>Patients</subject><subject>PD-L1 protein</subject><subject>Peptides</subject><subject>Receptors, Antigen, T-Cell, gamma-delta - metabolism</subject><subject>T cell receptors</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocyte Subsets - metabolism</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>T-Lymphocytes, Cytotoxic - metabolism</subject><subject>Transduction, Genetic</subject><subject>Treatment Outcome</subject><subject>Tumor necrosis factor-TNF</subject><subject>T‐cell receptor</subject><subject>Xenograft Model Antitumor Assays</subject><subject>Xenografts</subject><subject>Zoledronic acid</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kc1u1DAQxy1ERb848ALIEicOaf2VOHtBqlIKqCsh0eVsOc5411USBzvZsjcegXeB5-hD8CS4TanggKXxeDQ__T2jP0IvKDmh6ZwaHU-oKCh7gg4oF4tMElI8vX_LbEE420eHMV4TwguxEM_QPmeyJDkrD9DXc9hC64cO-hF7i3Xjh9FtAbuum3o_biDoYYdv3LjBl5e_vn1fVumiKeIAxlln8Kr6lMox6D42k4EG3_64_bnCBto2Yr3Wro8jbqd-jY3uDYS5c4z2rG4jPH_IR-jzxdtV9T5bfnz3oTpbZkYUkmWF5abMWc2kJBzSkqWQlllbA9cSJMuZhJpSUxMBvLS6IE0OxhiqNRMEKD9Cb2bdYao7aEzaM-hWDcF1OuyU10792-ndRq39VslClESQJPDqQSD4LxPEUV37KfRpZsVEXjJakgVL1OuZMsHHGMA-_kCJujNJJZPUvUmJffn3SI_kH1cScDoDN66F3f-VVHV2NUv-Bk1Qou8</recordid><startdate>202011</startdate><enddate>202011</enddate><creator>Ichiki, Yoshinobu</creator><creator>Shigematsu, Yoshiki</creator><creator>Baba, Tetsuro</creator><creator>Shiota, Hironobu</creator><creator>Fukuyama, Takashi</creator><creator>Nagata, Yoshika</creator><creator>So, Tetsuya</creator><creator>Yasuda, Manabu</creator><creator>Takenoyama, Mitsuhiro</creator><creator>Yasumoto, Kosei</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><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>8FE</scope><scope>8FH</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>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1293-6952</orcidid></search><sort><creationdate>202011</creationdate><title>Development of adoptive immunotherapy with KK‐LC‐1‐specific TCR‐transduced γδT cells against lung cancer cells</title><author>Ichiki, Yoshinobu ; Shigematsu, Yoshiki ; Baba, Tetsuro ; Shiota, Hironobu ; Fukuyama, Takashi ; Nagata, Yoshika ; So, Tetsuya ; Yasuda, Manabu ; Takenoyama, Mitsuhiro ; Yasumoto, Kosei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4672-6f3c852b27703e146847f2ffbe3a7e72527eb11cb04e38fa60d5eccc1aa240e13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adenocarcinoma</topic><topic>Adoptive immunotherapy</topic><topic>Animals</topic><topic>Antigens</topic><topic>Antigens, Neoplasm - immunology</topic><topic>Antitumor activity</topic><topic>Apoptosis</topic><topic>CD8 antigen</topic><topic>Cell Line, Tumor</topic><topic>Cervical cancer</topic><topic>Cloning</topic><topic>CTL</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Cytotoxicity</topic><topic>Disease Models, Animal</topic><topic>FasL</topic><topic>FasL protein</topic><topic>Flow cytometry</topic><topic>Genes</topic><topic>Growth inhibition</topic><topic>Histocompatibility antigen HLA</topic><topic>Humans</topic><topic>Immunomodulation</topic><topic>Immunotherapy</topic><topic>Immunotherapy, Adoptive</topic><topic>Injection</topic><topic>Interferon</topic><topic>KK‐LC‐1</topic><topic>Laboratories</topic><topic>Ligands</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - etiology</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - pathology</topic><topic>Lung Neoplasms - therapy</topic><topic>Lymphatic system</topic><topic>Lymphocytes</topic><topic>Lymphocytes B</topic><topic>Lymphocytes, Tumor-Infiltrating - immunology</topic><topic>Lymphocytes, Tumor-Infiltrating - metabolism</topic><topic>Lymphocytes, Tumor-Infiltrating - pathology</topic><topic>Metastasis</topic><topic>Mice, Transgenic</topic><topic>Original</topic><topic>Patients</topic><topic>PD-L1 protein</topic><topic>Peptides</topic><topic>Receptors, Antigen, T-Cell, gamma-delta - metabolism</topic><topic>T cell receptors</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>T-Lymphocyte Subsets - metabolism</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>T-Lymphocytes, Cytotoxic - metabolism</topic><topic>Transduction, Genetic</topic><topic>Treatment Outcome</topic><topic>Tumor necrosis factor-TNF</topic><topic>T‐cell receptor</topic><topic>Xenograft Model Antitumor Assays</topic><topic>Xenografts</topic><topic>Zoledronic acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ichiki, Yoshinobu</creatorcontrib><creatorcontrib>Shigematsu, Yoshiki</creatorcontrib><creatorcontrib>Baba, Tetsuro</creatorcontrib><creatorcontrib>Shiota, Hironobu</creatorcontrib><creatorcontrib>Fukuyama, Takashi</creatorcontrib><creatorcontrib>Nagata, Yoshika</creatorcontrib><creatorcontrib>So, Tetsuya</creatorcontrib><creatorcontrib>Yasuda, Manabu</creatorcontrib><creatorcontrib>Takenoyama, Mitsuhiro</creatorcontrib><creatorcontrib>Yasumoto, Kosei</creatorcontrib><collection>Wiley Online Library (Open Access Collection)</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Access via ProQuest (Open Access)</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>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ichiki, Yoshinobu</au><au>Shigematsu, Yoshiki</au><au>Baba, Tetsuro</au><au>Shiota, Hironobu</au><au>Fukuyama, Takashi</au><au>Nagata, Yoshika</au><au>So, Tetsuya</au><au>Yasuda, Manabu</au><au>Takenoyama, Mitsuhiro</au><au>Yasumoto, Kosei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of adoptive immunotherapy with KK‐LC‐1‐specific TCR‐transduced γδT cells against lung cancer cells</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2020-11</date><risdate>2020</risdate><volume>111</volume><issue>11</issue><spage>4021</spage><epage>4030</epage><pages>4021-4030</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>The present study analyzed the antitumor effect of γδT cells transduced with the TCR of cancer‐specific CTLs to establish forceful cancer‐specific adoptive immunotherapy. We cloned the TCRαβ genes from CTLs showing HLA‐B15 restricted recognition of Kita‐Kyushu lung cancer antigen‐1 (KK‐LC‐1), a cancer/germline gene antigen, identified in a lung adenocarcinoma case (F1121). The TCRαβ and CD8 genes were transduced into γδT cells induced from PBLs of healthy volunteers stimulated with zoledronate and IL‐2. The KK‐LC‐1‐specific TCRαβ‐CD8 γδT cells showed cytotoxic activity against the KK‐LC‐1 positive lung cancer cell line F1121L and produced IFN‐γ against F1121L and KK‐LC‐1 peptide‐pulsed F1121 EBV‐B cells. These responses were blocked by HLA class I and HLA‐B/C antibodies. An in vivo assay using NOD/SCID mice with xenotransplantation of human lung cancer cells was performed, and the TCRαβ‐CD8 transduced γδT cells (TCRαβ‐CD8 γδT cells) were intravenously injected. Growth inhibition of KK‐LC‐1+, HLA‐B15+ lung cancer cells was confirmed in mice with injection of the TCRαβ‐CD8 γδT cells from 1 wk after xenotransplantation of cancer cells but not in those treated 2 wk after xenotransplantation. The resected specimens of the tumor, 2 wk after xenotransplantation, highly expressed FasL but not programmed death ligand‐1 (PD‐L1) by immunohistochemical staining. FasL highly expressed cancer cells xenotransplanted 2 wk ago were resistant to TCRαβ‐CD8 γδT cells injection. These results suggested that apoptosis of Fas‐positive TCRαβ‐CD8 γδT cells may be induced by a Fas‐mediated signal after interacting with FasL‐positive cancer cells.
(1) Kita‐Kyushu lung cancer antigen‐1 (KK‐LC‐1)‐specific cytotoxicity, which is the same as that observed in CTL clones, was obtained by transducing KK‐LC‐1‐specific TCRαβ and CD8 cells into γδT cells. (2) An in vivo assay using NOD/SCID mice with xenotransplantation of human lung cancer cells was performed, and the TCRαβ‐CD8 transduced γδT cells were intravenously injected. Growth inhibition of KK‐LC‐1+, HLA‐B15+ lung cancer cells was observed in mice with tumors 1 wk after xenotransplantation but not in those mice with tumors 2 wk after xenotransplantation. (3) Cancer cells expressed a high level of FasL at 2 wk after xenotransplantation and escaped adoptive treatment. We should be alert for Fas‐mediated apoptosis when applying such cellular immunotherapy.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>32780528</pmid><doi>10.1111/cas.14612</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-1293-6952</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1347-9032 |
| ispartof | Cancer science, 2020-11, Vol.111 (11), p.4021-4030 |
| issn | 1347-9032 1349-7006 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7648040 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Access via Wiley Online Library; Wiley Online Library (Open Access Collection); PubMed Central |
| subjects | Adenocarcinoma Adoptive immunotherapy Animals Antigens Antigens, Neoplasm - immunology Antitumor activity Apoptosis CD8 antigen Cell Line, Tumor Cervical cancer Cloning CTL Cytokines Cytokines - metabolism Cytotoxicity Disease Models, Animal FasL FasL protein Flow cytometry Genes Growth inhibition Histocompatibility antigen HLA Humans Immunomodulation Immunotherapy Immunotherapy, Adoptive Injection Interferon KK‐LC‐1 Laboratories Ligands Lung cancer Lung Neoplasms - etiology Lung Neoplasms - metabolism Lung Neoplasms - pathology Lung Neoplasms - therapy Lymphatic system Lymphocytes Lymphocytes B Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - metabolism Lymphocytes, Tumor-Infiltrating - pathology Metastasis Mice, Transgenic Original Patients PD-L1 protein Peptides Receptors, Antigen, T-Cell, gamma-delta - metabolism T cell receptors T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism T-Lymphocytes, Cytotoxic - immunology T-Lymphocytes, Cytotoxic - metabolism Transduction, Genetic Treatment Outcome Tumor necrosis factor-TNF T‐cell receptor Xenograft Model Antitumor Assays Xenografts Zoledronic acid |
| title | Development of adoptive immunotherapy with KK‐LC‐1‐specific TCR‐transduced γδT cells against lung cancer cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T02%3A01%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Development%20of%20adoptive%20immunotherapy%20with%20KK%E2%80%90LC%E2%80%901%E2%80%90specific%20TCR%E2%80%90transduced%20%CE%B3%CE%B4T%20cells%20against%20lung%20cancer%20cells&rft.jtitle=Cancer%20science&rft.au=Ichiki,%20Yoshinobu&rft.date=2020-11&rft.volume=111&rft.issue=11&rft.spage=4021&rft.epage=4030&rft.pages=4021-4030&rft.issn=1347-9032&rft.eissn=1349-7006&rft_id=info:doi/10.1111/cas.14612&rft_dat=%3Cproquest_pubme%3E2458218092%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2458218092&rft_id=info:pmid/32780528&rfr_iscdi=true |