Robust expansion of viral antigen-specific CD4+ and CD8+ T cells for adoptive T cell therapy using gene-modified activated T cells as antigen presenting cells
Identifieur interne : 002E63 ( Main/Exploration ); précédent : 002E62; suivant : 002E64Robust expansion of viral antigen-specific CD4+ and CD8+ T cells for adoptive T cell therapy using gene-modified activated T cells as antigen presenting cells
Auteurs : Jan Joseph Melenhorst [États-Unis] ; Scott Robert Solomon [États-Unis] ; Aarthi Shenoy [États-Unis] ; Nancy Fern Hensel [États-Unis] ; John Philip Jr Mccoy [États-Unis] ; Keyvan Keyvanfar [États-Unis] ; Austin John Barrett [États-Unis]Source :
- Journal of immunotherapy : (1997) [ 1524-9557 ] ; 2006.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Génétique.
English descriptors
- KwdEn :
Abstract
Cytomegalovirus (CMV) reactivation after stem cell transplantation can be treated with CMV-specific T cells, but current in vitro techniques using dendritic cells as antigen-presenting cells are time-consuming and expensive. To simplify the production of clinical grade CMV-specific T cells, we evaluated gene-modified activated T cells [antigen presenting T cells (T-APCs)] as a reliable and easily produced source of APCs to boost CD4+ and CD8+ T-cell responses against the immunodominant CMV antigen pp65. T-APCs expressing the full-length immunodominant CMV pp65 gene were used to stimulate the expansion of autologous T cells. After 10 to 14 days, the T cell lines were tested for antigen specificity by using the flow cytometric intracellular detection of interferon-y after stimulation for 6 hours with a pp65 peptide library of 15-mers, overlapping by 11 amino acids. Under optimal conditions, this technique induced a median 766-fold and a 652-fold expansion of pp65-specific CD4+ and CD8+ responder cells, respectively, in 15 T cell lines. In 13 of 15 T cell lines, over 106 antigen-specific CD4+ plus CD8+ T cells were generated starting with only 5 x 106 peripheral blood mononuclear cells, representing an over 3-log increase. These data indicate that T-APCs efficiently boost pp65-specific CD4+ and CD8+ T cell numbers to clinically useful levels. The approach has the advantage of using a single leukocyte collection from the donor to generate large numbers of CMV-specific T cells within a total 3-week culture period using only one stimulation of antigen.
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type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Solomon, Scott Robert" sort="Solomon, Scott Robert" uniqKey="Solomon S" first="Scott Robert" last="Solomon">Scott Robert Solomon</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Stem Cell Allogeneic Transplantation Section, Hematology Branch, NHLBI, NIH, 10 Center Drive</s1><s2>Bethesda, MD 20892-1202</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Shenoy, Aarthi" sort="Shenoy, Aarthi" uniqKey="Shenoy A" first="Aarthi" last="Shenoy">Aarthi Shenoy</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Stem Cell Allogeneic Transplantation Section, Hematology Branch, NHLBI, NIH, 10 Center Drive</s1><s2>Bethesda, MD 20892-1202</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Fern Hensel, Nancy" sort="Fern Hensel, Nancy" uniqKey="Fern Hensel N" first="Nancy" last="Fern Hensel">Nancy Fern Hensel</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Stem Cell Allogeneic Transplantation Section, Hematology Branch, NHLBI, NIH, 10 Center Drive</s1><s2>Bethesda, MD 20892-1202</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Mccoy, John Philip Jr" sort="Mccoy, John Philip Jr" uniqKey="Mccoy J" first="John Philip Jr" last="Mccoy">John Philip Jr Mccoy</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Stem Cell Allogeneic Transplantation Section, Hematology Branch, NHLBI, NIH, 10 Center Drive</s1><s2>Bethesda, MD 20892-1202</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Keyvanfar, Keyvan" sort="Keyvanfar, Keyvan" uniqKey="Keyvanfar K" first="Keyvan" last="Keyvanfar">Keyvan Keyvanfar</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Stem Cell Allogeneic Transplantation Section, Hematology Branch, NHLBI, NIH, 10 Center Drive</s1><s2>Bethesda, MD 20892-1202</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Barrett, Austin John" sort="Barrett, Austin John" uniqKey="Barrett A" first="Austin John" last="Barrett">Austin John Barrett</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Stem Cell Allogeneic Transplantation Section, Hematology Branch, NHLBI, NIH, 10 Center Drive</s1><s2>Bethesda, MD 20892-1202</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Maryland</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Journal of immunotherapy : (1997)</title><title level="j" type="abbreviated">J. immunother. : (1997)</title><idno type="ISSN">1524-9557</idno><imprint><date when="2006">2006</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Journal of immunotherapy : (1997)</title><title level="j" type="abbreviated">J. immunother. : (1997)</title><idno type="ISSN">1524-9557</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Accessory cell</term><term>Adoptive immunization</term><term>Antigen presenting cell</term><term>Cytomegalovirus</term><term>Expansion</term><term>Gene</term><term>Genetic transfer</term><term>Genetics</term><term>Helper cell</term><term>Immunotherapy</term><term>Instability</term><term>T-Lymphocyte</term><term>Treatment</term><term>Viral disease</term><term>Virus</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Instabilité</term><term>Expansion</term><term>Virus</term><term>Virose</term><term>Cellule helper</term><term>Lymphocyte T</term><term>Immunisation adoptive</term><term>Immunothérapie</term><term>Gène</term><term>Génétique</term><term>Cellule accessoire</term><term>Cellule APC</term><term>Cytomegalovirus</term><term>Transfert génétique</term><term>Traitement</term><term>Antigène CD8</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Cytomegalovirus (CMV) reactivation after stem cell transplantation can be treated with CMV-specific T cells, but current in vitro techniques using dendritic cells as antigen-presenting cells are time-consuming and expensive. To simplify the production of clinical grade CMV-specific T cells, we evaluated gene-modified activated T cells [antigen presenting T cells (T-APCs)] as a reliable and easily produced source of APCs to boost CD4<sup>+</sup> and CD8<sup>+</sup> T-cell responses against the immunodominant CMV antigen pp65. T-APCs expressing the full-length immunodominant CMV pp65 gene were used to stimulate the expansion of autologous T cells. After 10 to 14 days, the T cell lines were tested for antigen specificity by using the flow cytometric intracellular detection of interferon-y after stimulation for 6 hours with a pp65 peptide library of 15-mers, overlapping by 11 amino acids. Under optimal conditions, this technique induced a median 766-fold and a 652-fold expansion of pp65-specific CD4<sup>+</sup> and CD8<sup>+</sup> responder cells, respectively, in 15 T cell lines. In 13 of 15 T cell lines, over 10<sup>6</sup> antigen-specific CD4<sup>+</sup> plus CD8<sup>+</sup> T cells were generated starting with only 5 x 10<sup>6</sup> peripheral blood mononuclear cells, representing an over 3-log increase. These data indicate that T-APCs efficiently boost pp65-specific CD4<sup>+</sup> and CD8<sup>+</sup> T cell numbers to clinically useful levels. The approach has the advantage of using a single leukocyte collection from the donor to generate large numbers of CMV-specific T cells within a total 3-week culture period using only one stimulation of antigen.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Melenhorst, Jan Joseph" sort="Melenhorst, Jan Joseph" uniqKey="Melenhorst J" first="Jan Joseph" last="Melenhorst">Jan Joseph Melenhorst</name></region><name sortKey="Barrett, Austin John" sort="Barrett, Austin John" uniqKey="Barrett A" first="Austin John" last="Barrett">Austin John Barrett</name><name sortKey="Fern Hensel, Nancy" sort="Fern Hensel, Nancy" uniqKey="Fern Hensel N" first="Nancy" last="Fern Hensel">Nancy Fern Hensel</name><name sortKey="Keyvanfar, Keyvan" sort="Keyvanfar, Keyvan" uniqKey="Keyvanfar K" first="Keyvan" last="Keyvanfar">Keyvan Keyvanfar</name><name sortKey="Mccoy, John Philip Jr" sort="Mccoy, John Philip Jr" uniqKey="Mccoy J" first="John Philip Jr" last="Mccoy">John Philip Jr Mccoy</name><name sortKey="Shenoy, Aarthi" sort="Shenoy, Aarthi" uniqKey="Shenoy A" first="Aarthi" last="Shenoy">Aarthi Shenoy</name><name sortKey="Solomon, Scott Robert" sort="Solomon, Scott Robert" uniqKey="Solomon S" first="Scott Robert" last="Solomon">Scott Robert Solomon</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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