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| 001 | 300766 | ||
| 005 | 20250511020452.0 | ||
| 024 | 7 | _ | |a 10.1136/jitc-2024-011351 |2 doi |
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| 024 | 7 | _ | |a pmc:PMC12049912 |2 pmc |
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| 037 | _ | _ | |a DKFZ-2025-00914 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Rosenberger, Leonie |b 0 |
| 245 | _ | _ | |a Selection of therapeutically effective T-cell receptors from the diverse tumor-bearing repertoire. |
| 260 | _ | _ | |a London |c 2025 |b BioMed Central |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1746449525_29662 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a The development of T-cell receptor (TCR)-based T-cell therapies is hampered by the difficulties in identifying therapeutically effective tumor-specific TCRs from the natural repertoire of a patient's cancer-specific T cells.Here, we mimic experimentally near-patient conditions to analyze the T-cell repertoire in euthymic tumor-bearing mice responding to the H-2Kb-presented neoantigen p68S551F (mp68). We temporarily separated the time point of mp68 expression from that of cancer cell transplantation to exclude the influence of injection-induced inflammation on T-cell priming. Thus, the mp68-specific T-cell response could only develop after the acute inflammatory phase had subsided.We found that mp68-specific TCRs isolated from either tumor-infiltrating T cells or spleens of mice immunized with mp68-expressing cancer cells are diverse and not inherently therapeutic when introduced into peripheral T cells and used for adoptive therapy of established tumors. While measuring short-term T-cell responses in vitro was unreliable for some TCRs in predicting their therapeutic failure, assessing the persistence of cancer cell destruction by TCR-modified T cells in long-term cultures accurately predicted therapeutic outcomes. A tumor-derived TCR with optimal function was also correctly identified with this approach when analyzing human TCRs that recognize the HLA-A2-presented neoantigen CDK4R24L.We show that a neoantigen-directed T-cell response in tumor-bearing hosts comprises a diverse repertoire. Infiltration and expansion of certain T-cell clonotypes in the tumor do not necessarily correlate with therapeutic efficacy of their TCRs in adoptive therapy. We propose that analysis of persistent rather than immediate responses of TCR-modified T cells in vitro serves as a reliable parameter to identify TCRs that are therapeutically effective in vivo. |
| 536 | _ | _ | |a 899 - ohne Topic (POF4-899) |0 G:(DE-HGF)POF4-899 |c POF4-899 |f POF IV |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de |
| 650 | _ | 7 | |a Adoptive cell therapy - ACT |2 Other |
| 650 | _ | 7 | |a Immunotherapy |2 Other |
| 650 | _ | 7 | |a T cell |2 Other |
| 650 | _ | 7 | |a T cell Receptor - TCR |2 Other |
| 650 | _ | 7 | |a Tumor infiltrating lymphocyte - TIL |2 Other |
| 650 | _ | 7 | |a Receptors, Antigen, T-Cell |2 NLM Chemicals |
| 650 | _ | 7 | |a Antigens, Neoplasm |2 NLM Chemicals |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Receptors, Antigen, T-Cell: immunology |2 MeSH |
| 650 | _ | 2 | |a Receptors, Antigen, T-Cell: metabolism |2 MeSH |
| 650 | _ | 2 | |a Receptors, Antigen, T-Cell: genetics |2 MeSH |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a Immunotherapy, Adoptive: methods |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a T-Lymphocytes: immunology |2 MeSH |
| 650 | _ | 2 | |a Antigens, Neoplasm: immunology |2 MeSH |
| 650 | _ | 2 | |a Cell Line, Tumor |2 MeSH |
| 650 | _ | 2 | |a Neoplasms: immunology |2 MeSH |
| 650 | _ | 2 | |a Neoplasms: therapy |2 MeSH |
| 700 | 1 | _ | |a Hansmann, Leo Alexander |0 P:(DE-He78)31f25f8d7e96b0f9ebd5ace0075ed18e |b 1 |
| 700 | 1 | _ | |a Anastasopoulou, Vasiliki |0 P:(DE-He78)222b62b16ec30c0cc9c59d65cdc2e096 |b 2 |
| 700 | 1 | _ | |a Wolf, Steven P |0 0009-0008-2723-695X |b 3 |
| 700 | 1 | _ | |a Drousch, Kimberley |b 4 |
| 700 | 1 | _ | |a Moewes, Christina |b 5 |
| 700 | 1 | _ | |a Feng, Xinyi |b 6 |
| 700 | 1 | _ | |a Cao, Guoshuai |b 7 |
| 700 | 1 | _ | |a Huang, Jun |0 0000-0003-0271-4384 |b 8 |
| 700 | 1 | _ | |a Yew, Poh Yin |b 9 |
| 700 | 1 | _ | |a Strønen, Erlend |0 0000-0001-9314-9389 |b 10 |
| 700 | 1 | _ | |a Kato, Taigo |b 11 |
| 700 | 1 | _ | |a Saligrama, Naresha |b 12 |
| 700 | 1 | _ | |a Olweus, Johanna |b 13 |
| 700 | 1 | _ | |a Nakamura, Yusuke |b 14 |
| 700 | 1 | _ | |a Willimsky, Gerald |0 P:(DE-He78)bc039c65f54568c14d4aca488c101452 |b 15 |u dkfz |
| 700 | 1 | _ | |a Blankenstein, Thomas |b 16 |
| 700 | 1 | _ | |a Schreiber, Hans |b 17 |
| 700 | 1 | _ | |a Leisegang, Matthias |0 0000-0003-3692-7142 |b 18 |
| 773 | _ | _ | |a 10.1136/jitc-2024-011351 |g Vol. 13, no. 5, p. e011351 - |0 PERI:(DE-600)2719863-7 |n 5 |p e011351 |t Journal for ImmunoTherapy of Cancer |v 13 |y 2025 |x 2051-1426 |
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