Expression of a Chimeric Antigen Receptor in Multiple Leukocyte Lineages in Transgenic Mice
Identifieur interne : 002E13 ( Main/Exploration ); précédent : 002E12; suivant : 002E14Expression of a Chimeric Antigen Receptor in Multiple Leukocyte Lineages in Transgenic Mice
Auteurs : Carmen S. M. Yong [Australie] ; Jennifer A. Westwood [Australie] ; Jan Schröder [Australie] ; Anthony T. Papenfuss [Australie] ; Bianca Von Scheidt [Australie] ; Maria Moeller [Australie] ; Christel Devaud [Australie, France] ; Phillip K. Darcy [Australie] ; Michael H. Kershaw [Australie]Source :
- PLoS ONE [ 1932-6203 ] ; 2015.
Descripteurs français
- KwdFr :
- Animaux, Humains, Immunothérapie adoptive, Lignage cellulaire (immunologie), Lymphocytes T CD8+ (immunologie), Recovérine (biosynthèse), Recovérine (génétique), Recovérine (immunologie), Souris, Souris transgéniques, Thymocytes (immunologie), Thymus (glande) (immunologie), Transduction du signal, Tumeurs (), Tumeurs (immunologie).
- MESH :
- biosynthèse : Recovérine.
- génétique : Recovérine.
- immunologie : Lignage cellulaire, Lymphocytes T CD8+, Recovérine, Thymocytes, Thymus (glande), Tumeurs.
- Animaux, Humains, Immunothérapie adoptive, Souris, Souris transgéniques, Transduction du signal, Tumeurs.
English descriptors
- KwdEn :
- Animals, CD8-Positive T-Lymphocytes (immunology), Cell Lineage (immunology), Humans, Immunotherapy, Adoptive, Mice, Mice, Transgenic, Neoplasms (immunology), Neoplasms (therapy), Recoverin (biosynthesis), Recoverin (genetics), Recoverin (immunology), Signal Transduction, Thymocytes (immunology), Thymus Gland (immunology).
- MESH :
- chemical , biosynthesis : Recoverin.
- chemical , genetics : Recoverin.
- immunology : CD8-Positive T-Lymphocytes, Cell Lineage, Neoplasms, Recoverin, Thymocytes, Thymus Gland.
- therapy : Neoplasms.
- Animals, Humans, Immunotherapy, Adoptive, Mice, Mice, Transgenic, Signal Transduction.
Abstract
Genetically modified CD8+ T lymphocytes have shown significant anti-tumor effects in the adoptive immunotherapy of cancer, with recent studies highlighting a potential role for a combination of other immune subsets to enhance these results. However, limitations in present genetic modification techniques impose difficulties in our ability to fully explore the potential of various T cell subsets and assess the potential of other leukocytes armed with chimeric antigen receptors (CARs). To address this issue, we generated a transgenic mouse model using a pan-hematopoietic promoter (
Url:
DOI: 10.1371/journal.pone.0140543
PubMed: 26505904
PubMed Central: 4624721
Affiliations:
- Australie, France
- Midi-Pyrénées, Occitanie (région administrative), Victoria (État)
- Melbourne, Toulouse
- Université de Melbourne
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Le document en format XML
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M." last="Yong">Carmen S. M. Yong</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Westwood, Jennifer A" sort="Westwood, Jennifer A" uniqKey="Westwood J" first="Jennifer A." last="Westwood">Jennifer A. Westwood</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Schroder, Jan" sort="Schroder, Jan" uniqKey="Schroder J" first="Jan" last="Schröder">Jan Schröder</name><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052</wicri:regionArea><wicri:noRegion>3052</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Bioinformatics and Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Bioinformatics and Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002</wicri:regionArea><wicri:noRegion>3002</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff004"><addr-line>Department of Computing and Information Systems, The University of Melbourne, Parkville, Victoria, 3010, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Computing and Information Systems, The University of Melbourne, Parkville, Victoria, 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Papenfuss, Anthony T" sort="Papenfuss, Anthony T" uniqKey="Papenfuss A" first="Anthony T." last="Papenfuss">Anthony T. Papenfuss</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, Victoria, 3052</wicri:regionArea><wicri:noRegion>3052</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Bioinformatics and Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Bioinformatics and Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, Victoria, 3002</wicri:regionArea><wicri:noRegion>3002</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff004"><addr-line>Department of Computing and Information Systems, The University of Melbourne, Parkville, Victoria, 3010, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Computing and Information Systems, The University of Melbourne, Parkville, Victoria, 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff005"><addr-line>Department of Medical Biology, The University of Melbourne, Parkville, Victoria, 3010, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Biology, The University of Melbourne, Parkville, Victoria, 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Von Scheidt, Bianca" sort="Von Scheidt, Bianca" uniqKey="Von Scheidt B" first="Bianca" last="Von Scheidt">Bianca Von Scheidt</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Moeller, Maria" sort="Moeller, Maria" uniqKey="Moeller M" first="Maria" last="Moeller">Maria Moeller</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Devaud, Christel" sort="Devaud, Christel" uniqKey="Devaud C" first="Christel" last="Devaud">Christel Devaud</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation wicri:level="3"><nlm:aff id="aff006"><addr-line>INSERM U1043 Centre de Physiopathologie Toulouse Purpan (CPTP), Toulouse, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM U1043 Centre de Physiopathologie Toulouse Purpan (CPTP), Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Darcy, Phillip K" sort="Darcy, Phillip K" uniqKey="Darcy P" first="Phillip K." last="Darcy">Phillip K. Darcy</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation><nlm:aff id="aff007"><addr-line>Department of Immunology, Monash University, Prahran Victoria 3181 Australia</addr-line></nlm:aff><wicri:noCountry code="subfield">Prahran Victoria 3181 Australia</wicri:noCountry></affiliation></author><author><name sortKey="Kershaw, Michael H" sort="Kershaw, Michael H" uniqKey="Kershaw M" first="Michael H." last="Kershaw">Michael H. Kershaw</name><affiliation wicri:level="4"><nlm:aff id="aff001"><addr-line>Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation><affiliation><nlm:aff id="aff007"><addr-line>Department of Immunology, Monash University, Prahran Victoria 3181 Australia</addr-line></nlm:aff><wicri:noCountry code="subfield">Prahran Victoria 3181 Australia</wicri:noCountry></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>CD8-Positive T-Lymphocytes (immunology)</term><term>Cell Lineage (immunology)</term><term>Humans</term><term>Immunotherapy, Adoptive</term><term>Mice</term><term>Mice, Transgenic</term><term>Neoplasms (immunology)</term><term>Neoplasms (therapy)</term><term>Recoverin (biosynthesis)</term><term>Recoverin (genetics)</term><term>Recoverin (immunology)</term><term>Signal Transduction</term><term>Thymocytes (immunology)</term><term>Thymus Gland (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Humains</term><term>Immunothérapie adoptive</term><term>Lignage cellulaire (immunologie)</term><term>Lymphocytes T CD8+ (immunologie)</term><term>Recovérine (biosynthèse)</term><term>Recovérine (génétique)</term><term>Recovérine (immunologie)</term><term>Souris</term><term>Souris transgéniques</term><term>Thymocytes (immunologie)</term><term>Thymus (glande) (immunologie)</term><term>Transduction du signal</term><term>Tumeurs ()</term><term>Tumeurs (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Recoverin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Recoverin</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Recovérine</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Recovérine</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Lignage cellulaire</term><term>Lymphocytes T CD8+</term><term>Recovérine</term><term>Thymocytes</term><term>Thymus (glande)</term><term>Tumeurs</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term><term>Cell Lineage</term><term>Neoplasms</term><term>Recoverin</term><term>Thymocytes</term><term>Thymus Gland</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Neoplasms</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Humans</term><term>Immunotherapy, Adoptive</term><term>Mice</term><term>Mice, Transgenic</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Humains</term><term>Immunothérapie adoptive</term><term>Souris</term><term>Souris transgéniques</term><term>Transduction du signal</term><term>Tumeurs</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Genetically modified CD8<sup>+</sup> T lymphocytes have shown significant anti-tumor effects in the adoptive immunotherapy of cancer, with recent studies highlighting a potential role for a combination of other immune subsets to enhance these results. However, limitations in present genetic modification techniques impose difficulties in our ability to fully explore the potential of various T cell subsets and assess the potential of other leukocytes armed with chimeric antigen receptors (CARs). To address this issue, we generated a transgenic mouse model using a pan-hematopoietic promoter (<italic>vav</italic>) to drive the expression of a CAR specific for a tumor antigen. Here we present a characterization of the immune cell compartment in two unique <italic>vav</italic>-CAR transgenic mice models, Founder 9 (F9) and Founder 38 (F38). We demonstrate the <italic>vav</italic> promoter is indeed capable of driving the expression of a CAR in cells from both myeloid and lymphoid lineage, however the highest level of expression was observed in T lymphocytes from F38 mice. Lymphoid organs in <italic>vav</italic>-CAR mice were smaller and had reduced cell numbers compared to the wild type (WT) controls. Furthermore, the immune composition of F9 mice differed greatly with a significant reduction in lymphocytes found in the thymus, lymph node and spleen of these mice. To gain insight into the altered immune phenotype of F9 mice, we determined the chromosomal integration site of the transgene in both mouse strains using whole genome sequencing (WGS). We demonstrated that compared to the 7 copies found in F38 mice, F9 mice harbored almost 270 copies. These novel <italic>vav-</italic>CAR models provide a ready source of CAR expressing myeloid and lymphoid cells and will aid in facilitating future experiments to delineate the role for other leukocytes for adoptive immunotherapy against cancer.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Lahl, K" uniqKey="Lahl K">K Lahl</name></author><author><name sortKey="Sparwasser, T" uniqKey="Sparwasser T">T Sparwasser</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hogquist, Ka" uniqKey="Hogquist K">KA Hogquist</name></author><author><name sortKey="Jameson, Sc" uniqKey="Jameson S">SC Jameson</name></author><author><name sortKey="Heath, Wr" uniqKey="Heath W">WR Heath</name></author><author><name sortKey="Howard, Jl" uniqKey="Howard J">JL Howard</name></author><author><name sortKey="Bevan, Mj" uniqKey="Bevan M">MJ Bevan</name></author><author><name sortKey="Carbone, Fr" uniqKey="Carbone F">FR 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sortKey="Salzberg, Sl" uniqKey="Salzberg S">SL Salzberg</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Midi-Pyrénées</li><li>Occitanie (région administrative)</li><li>Victoria (État)</li></region><settlement><li>Melbourne</li><li>Toulouse</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="Australie"><region name="Victoria (État)"><name sortKey="Yong, Carmen S M" sort="Yong, Carmen S M" uniqKey="Yong C" first="Carmen S. M." last="Yong">Carmen S. M. Yong</name></region><name sortKey="Darcy, Phillip K" sort="Darcy, Phillip K" uniqKey="Darcy P" first="Phillip K." last="Darcy">Phillip K. Darcy</name><name sortKey="Devaud, Christel" sort="Devaud, Christel" uniqKey="Devaud C" first="Christel" last="Devaud">Christel Devaud</name><name sortKey="Kershaw, Michael H" sort="Kershaw, Michael H" uniqKey="Kershaw M" first="Michael H." last="Kershaw">Michael H. Kershaw</name><name sortKey="Moeller, Maria" sort="Moeller, Maria" uniqKey="Moeller M" first="Maria" last="Moeller">Maria Moeller</name><name sortKey="Papenfuss, Anthony T" sort="Papenfuss, Anthony T" uniqKey="Papenfuss A" first="Anthony T." last="Papenfuss">Anthony T. Papenfuss</name><name sortKey="Papenfuss, Anthony T" sort="Papenfuss, Anthony T" uniqKey="Papenfuss A" first="Anthony T." last="Papenfuss">Anthony T. Papenfuss</name><name sortKey="Papenfuss, Anthony T" sort="Papenfuss, Anthony T" uniqKey="Papenfuss A" first="Anthony T." last="Papenfuss">Anthony T. Papenfuss</name><name sortKey="Papenfuss, Anthony T" sort="Papenfuss, Anthony T" uniqKey="Papenfuss A" first="Anthony T." last="Papenfuss">Anthony T. Papenfuss</name><name sortKey="Papenfuss, Anthony T" sort="Papenfuss, Anthony T" uniqKey="Papenfuss A" first="Anthony T." last="Papenfuss">Anthony T. Papenfuss</name><name sortKey="Schroder, Jan" sort="Schroder, Jan" uniqKey="Schroder J" first="Jan" last="Schröder">Jan Schröder</name><name sortKey="Schroder, Jan" sort="Schroder, Jan" uniqKey="Schroder J" first="Jan" last="Schröder">Jan Schröder</name><name sortKey="Schroder, Jan" sort="Schroder, Jan" uniqKey="Schroder J" first="Jan" last="Schröder">Jan Schröder</name><name sortKey="Von Scheidt, Bianca" sort="Von Scheidt, Bianca" uniqKey="Von Scheidt B" first="Bianca" last="Von Scheidt">Bianca Von Scheidt</name><name sortKey="Westwood, Jennifer A" sort="Westwood, Jennifer A" uniqKey="Westwood J" first="Jennifer A." last="Westwood">Jennifer A. Westwood</name></country><country name="France"><region name="Occitanie (région administrative)"><name sortKey="Devaud, Christel" sort="Devaud, Christel" uniqKey="Devaud C" first="Christel" last="Devaud">Christel Devaud</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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