Evaluation of therapeutic targeting of CCR7 in acute graft-versus-host disease
Graft-versus-host disease (GVHD) is the main complication after allogeneic hematopoietic stem cell transplantation. We previously unveiled a correlation between proportions of C-C motif chemokine receptor 7 (CCR7) + T cells in the apheresis and the risk of developing GVHD. We wanted to evaluate in v...
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Veröffentlicht in: | Bone marrow transplantation (Basingstoke) 2020-10, Vol.55 (10), p.1935-1945 |
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container_issue | 10 |
container_start_page | 1935 |
container_title | Bone marrow transplantation (Basingstoke) |
container_volume | 55 |
creator | Cuesta-Mateos, Carlos Portero-Sainz, Itxaso García-Peydró, Marina Alcain, Juan Fuentes, Patricia Juárez-Sánchez, Raquel Pérez-García, Yaiza Mateu-Albero, Tamara Díaz-Fernández, Paula Vega-Piris, Lorena Sánchez-López, Blanca A. Marcos-Jiménez, Ana Cardeñoso, Laura Gómez-García de Soria, Valle Toribio, María Luisa Muñoz-Calleja, Cecilia |
description | Graft-versus-host disease (GVHD) is the main complication after allogeneic hematopoietic stem cell transplantation. We previously unveiled a correlation between proportions of C-C motif chemokine receptor 7 (CCR7)
+
T cells in the apheresis and the risk of developing GVHD. We wanted to evaluate in vivo whether apheresis with low proportion of CCR7
+
cells or treatment with an anti-human CCR7 monoclonal antibody (mAb) were suitable strategies to prevent or treat acute GVHD in preclinical xenogeneic models. Therapeutic anti-CCR7 mAb was the most effective strategy in both prophylactic and therapeutic settings where antibody drastically reduced in vivo lymphoid organ infiltration of donor CCR7
+
T cells, extended lifespan and solved clinical signs. The antibody neutralized in vitro migration of naïve and central memory T cells toward CCR7 ligands and depleted target CCR7
+
subsets through complement activation. Both mechanisms of action spared CCR7
−
subsets, including effector memory and effector memory CD45RA
+
T cells which may mediate graft versus leukemia effect and immunity against infections. Accordingly, the numbers of donor CCR7
+
T cells in the apheresis were not associated to cytomegalovirus reactivation or the recurrence of the underlying disease. These findings provide a promising new strategy to prevent and treat acute GVHD, a condition where new specific, safety and effective treatment is needed. |
doi_str_mv | 10.1038/s41409-020-0830-8 |
format | Article |
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+
T cells in the apheresis and the risk of developing GVHD. We wanted to evaluate in vivo whether apheresis with low proportion of CCR7
+
cells or treatment with an anti-human CCR7 monoclonal antibody (mAb) were suitable strategies to prevent or treat acute GVHD in preclinical xenogeneic models. Therapeutic anti-CCR7 mAb was the most effective strategy in both prophylactic and therapeutic settings where antibody drastically reduced in vivo lymphoid organ infiltration of donor CCR7
+
T cells, extended lifespan and solved clinical signs. The antibody neutralized in vitro migration of naïve and central memory T cells toward CCR7 ligands and depleted target CCR7
+
subsets through complement activation. Both mechanisms of action spared CCR7
−
subsets, including effector memory and effector memory CD45RA
+
T cells which may mediate graft versus leukemia effect and immunity against infections. Accordingly, the numbers of donor CCR7
+
T cells in the apheresis were not associated to cytomegalovirus reactivation or the recurrence of the underlying disease. These findings provide a promising new strategy to prevent and treat acute GVHD, a condition where new specific, safety and effective treatment is needed.</description><identifier>ISSN: 0268-3369</identifier><identifier>EISSN: 1476-5365</identifier><identifier>DOI: 10.1038/s41409-020-0830-8</identifier><identifier>PMID: 32086495</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/1 ; 13/2 ; 13/31 ; 631/250/1904 ; 631/250/98 ; 631/532/1542 ; 64/60 ; 692/699/1541/1990 ; 692/699/249/1529 ; 96/21 ; Antibodies ; Apheresis ; Biophysics ; CC chemokine receptors ; CCR7 protein ; CD45RA antigen ; Cell Biology ; Complement activation ; Cytomegalovirus ; Cytomegalovirus infections ; Diseases ; Effector cells ; Graft versus host disease ; Graft-versus-host reaction ; Grafting ; Health aspects ; Health services ; Hematology ; Hematopoietic stem cells ; Immunological memory ; Immunology ; Internal Medicine ; Leukemia ; Life Sciences & Biomedicine ; Life span ; Lymphocytes ; Lymphocytes T ; Medical research ; Medicine ; Medicine & Public Health ; Medicine, Experimental ; Memory cells ; Monoclonal antibodies ; Oncology ; Public Health ; Relapse ; Science & Technology ; Stem cell transplantation ; Stem Cells ; T cells ; Therapeutic targets ; Transplantation</subject><ispartof>Bone marrow transplantation (Basingstoke), 2020-10, Vol.55 (10), p.1935-1945</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020</rights><rights>COPYRIGHT 2020 Nature Publishing Group</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>7</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000514941300002</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c470t-a97b9c9fc5d55d3ccb7d6aa2b02fa0eb3f2b4accac7f7aab3ceb919aa35e44a43</citedby><cites>FETCH-LOGICAL-c470t-a97b9c9fc5d55d3ccb7d6aa2b02fa0eb3f2b4accac7f7aab3ceb919aa35e44a43</cites><orcidid>0000-0003-3282-3231 ; 0000-0003-4597-1022</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27931,27932,28255</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32086495$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cuesta-Mateos, Carlos</creatorcontrib><creatorcontrib>Portero-Sainz, Itxaso</creatorcontrib><creatorcontrib>García-Peydró, Marina</creatorcontrib><creatorcontrib>Alcain, Juan</creatorcontrib><creatorcontrib>Fuentes, Patricia</creatorcontrib><creatorcontrib>Juárez-Sánchez, Raquel</creatorcontrib><creatorcontrib>Pérez-García, Yaiza</creatorcontrib><creatorcontrib>Mateu-Albero, Tamara</creatorcontrib><creatorcontrib>Díaz-Fernández, Paula</creatorcontrib><creatorcontrib>Vega-Piris, Lorena</creatorcontrib><creatorcontrib>Sánchez-López, Blanca A.</creatorcontrib><creatorcontrib>Marcos-Jiménez, Ana</creatorcontrib><creatorcontrib>Cardeñoso, Laura</creatorcontrib><creatorcontrib>Gómez-García de Soria, Valle</creatorcontrib><creatorcontrib>Toribio, María Luisa</creatorcontrib><creatorcontrib>Muñoz-Calleja, Cecilia</creatorcontrib><title>Evaluation of therapeutic targeting of CCR7 in acute graft-versus-host disease</title><title>Bone marrow transplantation (Basingstoke)</title><addtitle>Bone Marrow Transplant</addtitle><addtitle>BONE MARROW TRANSPL</addtitle><addtitle>Bone Marrow Transplant</addtitle><description>Graft-versus-host disease (GVHD) is the main complication after allogeneic hematopoietic stem cell transplantation. We previously unveiled a correlation between proportions of C-C motif chemokine receptor 7 (CCR7)
+
T cells in the apheresis and the risk of developing GVHD. We wanted to evaluate in vivo whether apheresis with low proportion of CCR7
+
cells or treatment with an anti-human CCR7 monoclonal antibody (mAb) were suitable strategies to prevent or treat acute GVHD in preclinical xenogeneic models. Therapeutic anti-CCR7 mAb was the most effective strategy in both prophylactic and therapeutic settings where antibody drastically reduced in vivo lymphoid organ infiltration of donor CCR7
+
T cells, extended lifespan and solved clinical signs. The antibody neutralized in vitro migration of naïve and central memory T cells toward CCR7 ligands and depleted target CCR7
+
subsets through complement activation. Both mechanisms of action spared CCR7
−
subsets, including effector memory and effector memory CD45RA
+
T cells which may mediate graft versus leukemia effect and immunity against infections. Accordingly, the numbers of donor CCR7
+
T cells in the apheresis were not associated to cytomegalovirus reactivation or the recurrence of the underlying disease. These findings provide a promising new strategy to prevent and treat acute GVHD, a condition where new specific, safety and effective treatment is needed.</description><subject>13/1</subject><subject>13/2</subject><subject>13/31</subject><subject>631/250/1904</subject><subject>631/250/98</subject><subject>631/532/1542</subject><subject>64/60</subject><subject>692/699/1541/1990</subject><subject>692/699/249/1529</subject><subject>96/21</subject><subject>Antibodies</subject><subject>Apheresis</subject><subject>Biophysics</subject><subject>CC chemokine receptors</subject><subject>CCR7 protein</subject><subject>CD45RA antigen</subject><subject>Cell Biology</subject><subject>Complement activation</subject><subject>Cytomegalovirus</subject><subject>Cytomegalovirus infections</subject><subject>Diseases</subject><subject>Effector cells</subject><subject>Graft versus host disease</subject><subject>Graft-versus-host reaction</subject><subject>Grafting</subject><subject>Health aspects</subject><subject>Health services</subject><subject>Hematology</subject><subject>Hematopoietic stem cells</subject><subject>Immunological memory</subject><subject>Immunology</subject><subject>Internal Medicine</subject><subject>Leukemia</subject><subject>Life Sciences & Biomedicine</subject><subject>Life span</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Medicine, Experimental</subject><subject>Memory cells</subject><subject>Monoclonal antibodies</subject><subject>Oncology</subject><subject>Public Health</subject><subject>Relapse</subject><subject>Science & Technology</subject><subject>Stem cell transplantation</subject><subject>Stem Cells</subject><subject>T cells</subject><subject>Therapeutic 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of therapeutic targeting of CCR7 in acute graft-versus-host disease</title><author>Cuesta-Mateos, Carlos ; Portero-Sainz, Itxaso ; García-Peydró, Marina ; Alcain, Juan ; Fuentes, Patricia ; Juárez-Sánchez, Raquel ; Pérez-García, Yaiza ; Mateu-Albero, Tamara ; Díaz-Fernández, Paula ; Vega-Piris, Lorena ; Sánchez-López, Blanca A. ; Marcos-Jiménez, Ana ; Cardeñoso, Laura ; Gómez-García de Soria, Valle ; Toribio, María Luisa ; Muñoz-Calleja, 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Valle</au><au>Toribio, María Luisa</au><au>Muñoz-Calleja, Cecilia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of therapeutic targeting of CCR7 in acute graft-versus-host disease</atitle><jtitle>Bone marrow transplantation (Basingstoke)</jtitle><stitle>Bone Marrow Transplant</stitle><stitle>BONE MARROW TRANSPL</stitle><addtitle>Bone Marrow Transplant</addtitle><date>2020-10-01</date><risdate>2020</risdate><volume>55</volume><issue>10</issue><spage>1935</spage><epage>1945</epage><pages>1935-1945</pages><issn>0268-3369</issn><eissn>1476-5365</eissn><abstract>Graft-versus-host disease (GVHD) is the main complication after allogeneic hematopoietic stem cell transplantation. We previously unveiled a correlation between proportions of C-C motif chemokine receptor 7 (CCR7)
+
T cells in the apheresis and the risk of developing GVHD. We wanted to evaluate in vivo whether apheresis with low proportion of CCR7
+
cells or treatment with an anti-human CCR7 monoclonal antibody (mAb) were suitable strategies to prevent or treat acute GVHD in preclinical xenogeneic models. Therapeutic anti-CCR7 mAb was the most effective strategy in both prophylactic and therapeutic settings where antibody drastically reduced in vivo lymphoid organ infiltration of donor CCR7
+
T cells, extended lifespan and solved clinical signs. The antibody neutralized in vitro migration of naïve and central memory T cells toward CCR7 ligands and depleted target CCR7
+
subsets through complement activation. Both mechanisms of action spared CCR7
−
subsets, including effector memory and effector memory CD45RA
+
T cells which may mediate graft versus leukemia effect and immunity against infections. Accordingly, the numbers of donor CCR7
+
T cells in the apheresis were not associated to cytomegalovirus reactivation or the recurrence of the underlying disease. These findings provide a promising new strategy to prevent and treat acute GVHD, a condition where new specific, safety and effective treatment is needed.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32086495</pmid><doi>10.1038/s41409-020-0830-8</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-3282-3231</orcidid><orcidid>https://orcid.org/0000-0003-4597-1022</orcidid></addata></record> |
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recordid | cdi_gale_infotracmisc_A636481444 |
source | Web of Science - Science Citation Index Expanded - 2020<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
subjects | 13/1 13/2 13/31 631/250/1904 631/250/98 631/532/1542 64/60 692/699/1541/1990 692/699/249/1529 96/21 Antibodies Apheresis Biophysics CC chemokine receptors CCR7 protein CD45RA antigen Cell Biology Complement activation Cytomegalovirus Cytomegalovirus infections Diseases Effector cells Graft versus host disease Graft-versus-host reaction Grafting Health aspects Health services Hematology Hematopoietic stem cells Immunological memory Immunology Internal Medicine Leukemia Life Sciences & Biomedicine Life span Lymphocytes Lymphocytes T Medical research Medicine Medicine & Public Health Medicine, Experimental Memory cells Monoclonal antibodies Oncology Public Health Relapse Science & Technology Stem cell transplantation Stem Cells T cells Therapeutic targets Transplantation |
title | Evaluation of therapeutic targeting of CCR7 in acute graft-versus-host disease |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-09T07%3A45%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Evaluation%20of%20therapeutic%20targeting%20of%20CCR7%20in%20acute%20graft-versus-host%20disease&rft.jtitle=Bone%20marrow%20transplantation%20(Basingstoke)&rft.au=Cuesta-Mateos,%20Carlos&rft.date=2020-10-01&rft.volume=55&rft.issue=10&rft.spage=1935&rft.epage=1945&rft.pages=1935-1945&rft.issn=0268-3369&rft.eissn=1476-5365&rft_id=info:doi/10.1038/s41409-020-0830-8&rft_dat=%3Cgale_cross%3EA636481444%3C/gale_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2475041759&rft_id=info:pmid/32086495&rft_galeid=A636481444&rfr_iscdi=true |