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 : 002250 ( PubMed/Curation ); précédent : 002249; suivant : 002251Robust 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 ; Aarthi Shenoy ; Nancy Fern Hensel ; John Philip Mccoy ; Keyvan Keyvanfar ; Austin John BarrettSource :
- Journal of immunotherapy (Hagerstown, Md. : 1997) [ 1524-9557 ]
Descripteurs français
- KwdFr :
- Activation des lymphocytes, Antigènes viraux (biosynthèse), Antigènes viraux (génétique), Antigènes viraux (immunologie), Cellules présentatrices d'antigène (immunologie), Cytomegalovirus (immunologie), Humains, Immunothérapie adoptive, Infections à cytomégalovirus (), Infections à cytomégalovirus (sang), Lignée cellulaire, Lymphocytes T CD4+ (immunologie), Lymphocytes T CD8+ (immunologie), Phosphoprotéines (biosynthèse), Phosphoprotéines (génétique), Phosphoprotéines (immunologie), Protéines de la matrice virale (biosynthèse), Protéines de la matrice virale (génétique), Protéines de la matrice virale (immunologie), Transduction génétique.
- MESH :
- biosynthèse : Antigènes viraux, Phosphoprotéines, Protéines de la matrice virale.
- génétique : Antigènes viraux, Phosphoprotéines, Protéines de la matrice virale.
- immunologie : Antigènes viraux, Cellules présentatrices d'antigène, Cytomegalovirus, Lymphocytes T CD4+, Lymphocytes T CD8+, Phosphoprotéines, Protéines de la matrice virale.
- sang : Infections à cytomégalovirus.
- Activation des lymphocytes, Humains, Immunothérapie adoptive, Infections à cytomégalovirus, Lignée cellulaire, Transduction génétique.
English descriptors
- KwdEn :
- Antigen-Presenting Cells (immunology), Antigens, Viral (biosynthesis), Antigens, Viral (genetics), Antigens, Viral (immunology), CD4-Positive T-Lymphocytes (immunology), CD8-Positive T-Lymphocytes (immunology), Cell Line, Cytomegalovirus (immunology), Cytomegalovirus Infections (blood), Cytomegalovirus Infections (therapy), Humans, Immunotherapy, Adoptive, Lymphocyte Activation, Phosphoproteins (biosynthesis), Phosphoproteins (genetics), Phosphoproteins (immunology), Transduction, Genetic, Viral Matrix Proteins (biosynthesis), Viral Matrix Proteins (genetics), Viral Matrix Proteins (immunology).
- MESH :
- chemical , biosynthesis : Antigens, Viral, Phosphoproteins, Viral Matrix Proteins.
- chemical , genetics : Antigens, Viral, Phosphoproteins, Viral Matrix Proteins.
- blood : Cytomegalovirus Infections.
- immunology : Antigen-Presenting Cells, Antigens, Viral, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cytomegalovirus, Phosphoproteins, Viral Matrix Proteins.
- therapy : Cytomegalovirus Infections.
- Cell Line, Humans, Immunotherapy, Adoptive, Lymphocyte Activation, Transduction, Genetic.
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-gamma 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 10 antigen-specific CD4+ plus CD8+ T cells were generated starting with only 5x10 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.
DOI: 10.1097/01.cji.0000211302.52503.93
PubMed: 16799339
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melenhoj@nhlbi.nih.gov</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Stem Cell Allogeneic Transplantation Section, Hematology Branch, NHLBI, NIH, 10 Center Drive, Bethesda, MD 20892-1202</wicri:regionArea></affiliation></author><author><name sortKey="Solomon, Scott Robert" sort="Solomon, Scott Robert" uniqKey="Solomon S" first="Scott Robert" last="Solomon">Scott Robert Solomon</name></author><author><name sortKey="Shenoy, Aarthi" sort="Shenoy, Aarthi" uniqKey="Shenoy A" first="Aarthi" last="Shenoy">Aarthi Shenoy</name></author><author><name sortKey="Hensel, Nancy Fern" sort="Hensel, Nancy Fern" uniqKey="Hensel N" first="Nancy Fern" last="Hensel">Nancy Fern Hensel</name></author><author><name sortKey="Mccoy, John Philip" sort="Mccoy, John Philip" uniqKey="Mccoy J" first="John Philip" last="Mccoy">John Philip Mccoy</name></author><author><name sortKey="Keyvanfar, Keyvan" sort="Keyvanfar, Keyvan" uniqKey="Keyvanfar K" first="Keyvan" last="Keyvanfar">Keyvan Keyvanfar</name></author><author><name sortKey="Barrett, Austin John" sort="Barrett, Austin John" uniqKey="Barrett A" first="Austin John" last="Barrett">Austin John Barrett</name></author></analytic><series><title level="j">Journal of immunotherapy (Hagerstown, Md. : 1997)</title><idno type="ISSN">1524-9557</idno></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antigen-Presenting Cells (immunology)</term><term>Antigens, Viral (biosynthesis)</term><term>Antigens, Viral (genetics)</term><term>Antigens, Viral (immunology)</term><term>CD4-Positive T-Lymphocytes (immunology)</term><term>CD8-Positive T-Lymphocytes (immunology)</term><term>Cell Line</term><term>Cytomegalovirus (immunology)</term><term>Cytomegalovirus Infections (blood)</term><term>Cytomegalovirus Infections (therapy)</term><term>Humans</term><term>Immunotherapy, Adoptive</term><term>Lymphocyte Activation</term><term>Phosphoproteins (biosynthesis)</term><term>Phosphoproteins (genetics)</term><term>Phosphoproteins (immunology)</term><term>Transduction, Genetic</term><term>Viral Matrix Proteins (biosynthesis)</term><term>Viral Matrix Proteins (genetics)</term><term>Viral Matrix Proteins (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activation des lymphocytes</term><term>Antigènes viraux (biosynthèse)</term><term>Antigènes viraux (génétique)</term><term>Antigènes viraux (immunologie)</term><term>Cellules présentatrices d'antigène (immunologie)</term><term>Cytomegalovirus (immunologie)</term><term>Humains</term><term>Immunothérapie adoptive</term><term>Infections à cytomégalovirus ()</term><term>Infections à cytomégalovirus (sang)</term><term>Lignée cellulaire</term><term>Lymphocytes T CD4+ (immunologie)</term><term>Lymphocytes T CD8+ (immunologie)</term><term>Phosphoprotéines (biosynthèse)</term><term>Phosphoprotéines (génétique)</term><term>Phosphoprotéines (immunologie)</term><term>Protéines de la matrice virale (biosynthèse)</term><term>Protéines de la matrice virale (génétique)</term><term>Protéines de la matrice virale (immunologie)</term><term>Transduction génétique</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Antigens, Viral</term><term>Phosphoproteins</term><term>Viral Matrix Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Antigens, Viral</term><term>Phosphoproteins</term><term>Viral Matrix Proteins</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Antigènes viraux</term><term>Phosphoprotéines</term><term>Protéines de la matrice virale</term></keywords><keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Cytomegalovirus Infections</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Antigènes viraux</term><term>Phosphoprotéines</term><term>Protéines de la matrice virale</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigènes viraux</term><term>Cellules présentatrices d'antigène</term><term>Cytomegalovirus</term><term>Lymphocytes T CD4+</term><term>Lymphocytes T CD8+</term><term>Phosphoprotéines</term><term>Protéines de la matrice virale</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Antigen-Presenting Cells</term><term>Antigens, Viral</term><term>CD4-Positive T-Lymphocytes</term><term>CD8-Positive T-Lymphocytes</term><term>Cytomegalovirus</term><term>Phosphoproteins</term><term>Viral Matrix Proteins</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Infections à cytomégalovirus</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Cytomegalovirus Infections</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line</term><term>Humans</term><term>Immunotherapy, Adoptive</term><term>Lymphocyte Activation</term><term>Transduction, Genetic</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Activation des lymphocytes</term><term>Humains</term><term>Immunothérapie adoptive</term><term>Infections à cytomégalovirus</term><term>Lignée cellulaire</term><term>Transduction 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+ 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-gamma 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 10 antigen-specific CD4+ plus CD8+ T cells were generated starting with only 5x10 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.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">16799339</PMID><DateCompleted><Year>2006</Year><Month>09</Month><Day>28</Day></DateCompleted><DateRevised><Year>2008</Year><Month>03</Month><Day>18</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">1524-9557</ISSN><JournalIssue CitedMedium="Print"><Volume>29</Volume><Issue>4</Issue><PubDate><MedlineDate>2006 Jul-Aug</MedlineDate></PubDate></JournalIssue><Title>Journal of immunotherapy (Hagerstown, Md. : 1997)</Title><ISOAbbreviation>J. Immunother.</ISOAbbreviation></Journal><ArticleTitle>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.</ArticleTitle><Pagination><MedlinePgn>436-43; discussion 365-6</MedlinePgn></Pagination><Abstract><AbstractText>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-gamma 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 10 antigen-specific CD4+ plus CD8+ T cells were generated starting with only 5x10 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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Melenhorst</LastName><ForeName>Jan Joseph</ForeName><Initials>JJ</Initials><AffiliationInfo><Affiliation>Stem Cell Allogeneic Transplantation Section, Hematology Branch, NHLBI, NIH, 10 Center Drive, Bethesda, MD 20892-1202, USA. melenhoj@nhlbi.nih.gov</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Solomon</LastName><ForeName>Scott Robert</ForeName><Initials>SR</Initials></Author><Author ValidYN="Y"><LastName>Shenoy</LastName><ForeName>Aarthi</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Hensel</LastName><ForeName>Nancy Fern</ForeName><Initials>NF</Initials></Author><Author ValidYN="Y"><LastName>McCoy</LastName><ForeName>John Philip</ForeName><Initials>JP</Initials><Suffix>Jr</Suffix></Author><Author ValidYN="Y"><LastName>Keyvanfar</LastName><ForeName>Keyvan</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Barrett</LastName><ForeName>Austin John</ForeName><Initials>AJ</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Immunother</MedlineTA><NlmUniqueID>9706083</NlmUniqueID><ISSNLinking>1524-9557</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000956">Antigens, Viral</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010750">Phosphoproteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014763">Viral Matrix Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C065418">cytomegalovirus matrix protein 65kDa</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="CommentIn"><RefSource>J Immunother. 2006 Jul-Aug;29(4):365-6</RefSource><PMID Version="1">16799331</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000938" MajorTopicYN="N">Antigen-Presenting Cells</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000956" MajorTopicYN="N">Antigens, Viral</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015496" MajorTopicYN="N">CD4-Positive T-Lymphocytes</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018414" MajorTopicYN="N">CD8-Positive T-Lymphocytes</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003587" MajorTopicYN="N">Cytomegalovirus</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003586" MajorTopicYN="N">Cytomegalovirus Infections</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName><QualifierName UI="Q000628" MajorTopicYN="N">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016219" MajorTopicYN="Y">Immunotherapy, Adoptive</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008213" MajorTopicYN="N">Lymphocyte Activation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010750" MajorTopicYN="N">Phosphoproteins</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014161" MajorTopicYN="N">Transduction, Genetic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014763" MajorTopicYN="N">Viral Matrix Proteins</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2006</Year><Month>6</Month><Day>27</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2006</Year><Month>9</Month><Day>29</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2006</Year><Month>6</Month><Day>27</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">16799339</ArticleId><ArticleId IdType="doi">10.1097/01.cji.0000211302.52503.93</ArticleId><ArticleId IdType="pii">00002371-200607000-00010</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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