An antigen-targeted approach to adoptive transfer therapy of cancer.
Previous attempts to treat human malignancies by adoptive transfer of tumor-specific CTLs have been limited by the difficulty of isolating T cells of defined antigen specificity. The recent development of MHC class I/antigenic peptide tetrameric complexes that allow direct identification of antigen-...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1999
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| _version_ | 1826296274233589760 |
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| author | Valmori, D Pittet, M Rimoldi, D Liénard, D Dunbar, R Cerundolo, V Lejeune, F Cerottini, J Romero, P |
| author_facet | Valmori, D Pittet, M Rimoldi, D Liénard, D Dunbar, R Cerundolo, V Lejeune, F Cerottini, J Romero, P |
| author_sort | Valmori, D |
| collection | OXFORD |
| description | Previous attempts to treat human malignancies by adoptive transfer of tumor-specific CTLs have been limited by the difficulty of isolating T cells of defined antigen specificity. The recent development of MHC class I/antigenic peptide tetrameric complexes that allow direct identification of antigen-specific T cells has opened new possibilities for the isolation and in vitro expansion of tumor-specific T cells. In the present study, we have derived polyclonal monospecific cell lines from circulating Melan-A-specific CTL precursors of HLA-A*0201+ melanoma patients by combining stimulation with recently identified peptide analogues of the immunodominant epitope from the melanoma-associated antigen Melan-A with staining with fluorescent HLA-A*0201/Melan-A peptide tetramers. In vitro expansion of antigen-specific CD8+ T cells was monitored by flow cytometry with the fluorescent tetramers and anti-CD8 monoclonal antibody. This analysis revealed that Melan-A 26-35 peptide analogues were much more efficient than the parental peptides in stimulating a rapid in vitro expansion of antigen-specific CD8+ T cells. These cells were then isolated by tetramer-guided cell sorting and subsequently expanded in vitro by mitogen stimulation. The resulting polyclonal but monospecific CTLs fully cross-recognized the parental peptides and were able to efficiently lyse Melan-A-expressing tumor cells. Altogether, these results pave the way to a molecularly defined approach to antigen-specific adoptive transfer therapy of cancer. |
| first_indexed | 2024-03-07T04:13:49Z |
| format | Journal article |
| id | oxford-uuid:c8b76e43-5a64-4887-9abb-bc3f5fc18524 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:13:49Z |
| publishDate | 1999 |
| record_format | dspace |
| spelling | oxford-uuid:c8b76e43-5a64-4887-9abb-bc3f5fc185242022-03-27T06:54:10ZAn antigen-targeted approach to adoptive transfer therapy of cancer.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c8b76e43-5a64-4887-9abb-bc3f5fc18524EnglishSymplectic Elements at Oxford1999Valmori, DPittet, MRimoldi, DLiénard, DDunbar, RCerundolo, VLejeune, FCerottini, JRomero, PPrevious attempts to treat human malignancies by adoptive transfer of tumor-specific CTLs have been limited by the difficulty of isolating T cells of defined antigen specificity. The recent development of MHC class I/antigenic peptide tetrameric complexes that allow direct identification of antigen-specific T cells has opened new possibilities for the isolation and in vitro expansion of tumor-specific T cells. In the present study, we have derived polyclonal monospecific cell lines from circulating Melan-A-specific CTL precursors of HLA-A*0201+ melanoma patients by combining stimulation with recently identified peptide analogues of the immunodominant epitope from the melanoma-associated antigen Melan-A with staining with fluorescent HLA-A*0201/Melan-A peptide tetramers. In vitro expansion of antigen-specific CD8+ T cells was monitored by flow cytometry with the fluorescent tetramers and anti-CD8 monoclonal antibody. This analysis revealed that Melan-A 26-35 peptide analogues were much more efficient than the parental peptides in stimulating a rapid in vitro expansion of antigen-specific CD8+ T cells. These cells were then isolated by tetramer-guided cell sorting and subsequently expanded in vitro by mitogen stimulation. The resulting polyclonal but monospecific CTLs fully cross-recognized the parental peptides and were able to efficiently lyse Melan-A-expressing tumor cells. Altogether, these results pave the way to a molecularly defined approach to antigen-specific adoptive transfer therapy of cancer. |
| spellingShingle | Valmori, D Pittet, M Rimoldi, D Liénard, D Dunbar, R Cerundolo, V Lejeune, F Cerottini, J Romero, P An antigen-targeted approach to adoptive transfer therapy of cancer. |
| title | An antigen-targeted approach to adoptive transfer therapy of cancer. |
| title_full | An antigen-targeted approach to adoptive transfer therapy of cancer. |
| title_fullStr | An antigen-targeted approach to adoptive transfer therapy of cancer. |
| title_full_unstemmed | An antigen-targeted approach to adoptive transfer therapy of cancer. |
| title_short | An antigen-targeted approach to adoptive transfer therapy of cancer. |
| title_sort | antigen targeted approach to adoptive transfer therapy of cancer |
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