T cell re-targeting to EBV antigens following TCR gene transfer: CD28-containing receptors mediate enhanced antigen-specific IFNgamma production.
EBV is associated with a broad range of malignancies. Adoptive immunotherapy of these tumors with EBV-specific CTL proved useful. We generated a panel of primary human T cells specific to various EBV antigens (i.e. Epstein-Barr nuclear antigen 3A, 3B and BamHI-M leftward reading frame) via transfer...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2006
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| _version_ | 1826257011613892608 |
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| author | Schaft, N Lankiewicz, B Drexhage, J Berrevoets, C Moss, D Levitsky, V Bonneville, M Lee, S Mcmichael, A Gratama, J Bolhuis, R Willemsen, R Debets, R |
| author_facet | Schaft, N Lankiewicz, B Drexhage, J Berrevoets, C Moss, D Levitsky, V Bonneville, M Lee, S Mcmichael, A Gratama, J Bolhuis, R Willemsen, R Debets, R |
| author_sort | Schaft, N |
| collection | OXFORD |
| description | EBV is associated with a broad range of malignancies. Adoptive immunotherapy of these tumors with EBV-specific CTL proved useful. We generated a panel of primary human T cells specific to various EBV antigens (i.e. Epstein-Barr nuclear antigen 3A, 3B and BamHI-M leftward reading frame) via transfer of modified TCR genes that are either coupled to CD3zeta or Fc(epsilon)RIgamma. TCR-transduced T cells from 20-60% of donors (total number of 25) demonstrated specific lysis of EBV peptide-loaded target cells, whereas lymphoblastoid cell lines expressing native EBV antigens were not killed by any of the EBV-specific T cell populations. This non-responsiveness, confirmed at the level of nuclear factor of activated T cells activation, is not due to receptor configuration since identical receptor formats specific for melanoma antigens successfully re-targeted T cells to native melanoma cells. In an effort to generate a more potent receptor, we introduced a CD28 domain into one of the EBV-specific TCR. This TCR did not affect the cytotoxic response of re-targeted T cells, but dramatically enhanced antigen-specific IFNgamma production. We therefore conclude that these novel CD28-containing EBV-specific TCRs provide a basis for further development of TCR gene transfer to treat EBV-induced diseases. |
| first_indexed | 2024-03-06T18:11:21Z |
| format | Journal article |
| id | oxford-uuid:03233ce2-05a6-41cf-bc68-acca04d1e4fc |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:11:21Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:03233ce2-05a6-41cf-bc68-acca04d1e4fc2022-03-26T08:44:26ZT cell re-targeting to EBV antigens following TCR gene transfer: CD28-containing receptors mediate enhanced antigen-specific IFNgamma production.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:03233ce2-05a6-41cf-bc68-acca04d1e4fcEnglishSymplectic Elements at Oxford2006Schaft, NLankiewicz, BDrexhage, JBerrevoets, CMoss, DLevitsky, VBonneville, MLee, SMcmichael, AGratama, JBolhuis, RWillemsen, RDebets, REBV is associated with a broad range of malignancies. Adoptive immunotherapy of these tumors with EBV-specific CTL proved useful. We generated a panel of primary human T cells specific to various EBV antigens (i.e. Epstein-Barr nuclear antigen 3A, 3B and BamHI-M leftward reading frame) via transfer of modified TCR genes that are either coupled to CD3zeta or Fc(epsilon)RIgamma. TCR-transduced T cells from 20-60% of donors (total number of 25) demonstrated specific lysis of EBV peptide-loaded target cells, whereas lymphoblastoid cell lines expressing native EBV antigens were not killed by any of the EBV-specific T cell populations. This non-responsiveness, confirmed at the level of nuclear factor of activated T cells activation, is not due to receptor configuration since identical receptor formats specific for melanoma antigens successfully re-targeted T cells to native melanoma cells. In an effort to generate a more potent receptor, we introduced a CD28 domain into one of the EBV-specific TCR. This TCR did not affect the cytotoxic response of re-targeted T cells, but dramatically enhanced antigen-specific IFNgamma production. We therefore conclude that these novel CD28-containing EBV-specific TCRs provide a basis for further development of TCR gene transfer to treat EBV-induced diseases. |
| spellingShingle | Schaft, N Lankiewicz, B Drexhage, J Berrevoets, C Moss, D Levitsky, V Bonneville, M Lee, S Mcmichael, A Gratama, J Bolhuis, R Willemsen, R Debets, R T cell re-targeting to EBV antigens following TCR gene transfer: CD28-containing receptors mediate enhanced antigen-specific IFNgamma production. |
| title | T cell re-targeting to EBV antigens following TCR gene transfer: CD28-containing receptors mediate enhanced antigen-specific IFNgamma production. |
| title_full | T cell re-targeting to EBV antigens following TCR gene transfer: CD28-containing receptors mediate enhanced antigen-specific IFNgamma production. |
| title_fullStr | T cell re-targeting to EBV antigens following TCR gene transfer: CD28-containing receptors mediate enhanced antigen-specific IFNgamma production. |
| title_full_unstemmed | T cell re-targeting to EBV antigens following TCR gene transfer: CD28-containing receptors mediate enhanced antigen-specific IFNgamma production. |
| title_short | T cell re-targeting to EBV antigens following TCR gene transfer: CD28-containing receptors mediate enhanced antigen-specific IFNgamma production. |
| title_sort | t cell re targeting to ebv antigens following tcr gene transfer cd28 containing receptors mediate enhanced antigen specific ifngamma production |
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