Orthotopic T-Cell Receptor Replacement—An “Enabler” for TCR-Based Therapies
Natural adaptive immunity co-evolved with pathogens over millions of years, and adoptive transfer of non-engineered T cells to fight infections or cancer so far exhibits an exceptionally safe and functional therapeutic profile in clinical trials. However, the personalized nature of therapies using v...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/6/1367 |
| _version_ | 1797566472992587776 |
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| author | Kilian Schober Thomas R. Müller Dirk H. Busch |
| author_facet | Kilian Schober Thomas R. Müller Dirk H. Busch |
| author_sort | Kilian Schober |
| collection | DOAJ |
| description | Natural adaptive immunity co-evolved with pathogens over millions of years, and adoptive transfer of non-engineered T cells to fight infections or cancer so far exhibits an exceptionally safe and functional therapeutic profile in clinical trials. However, the personalized nature of therapies using virus-specific T cells, donor lymphocyte infusion, or tumor-infiltrating lymphocytes makes implementation in routine clinical care difficult. In principle, genetic engineering can be used to make T-cell therapies more broadly applicable, but so far it significantly alters the physiology of cells. We recently demonstrated that orthotopic T-cell receptor (TCR) replacement (OTR) by clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR-associated protein 9 (Cas9) can be used to generate engineered T cells with preservation of near-physiological function. In this review, we present the current status of OTR technology development and discuss its potential for TCR-based therapies. By providing the means to combine the therapeutic efficacy and safety profile of physiological T cells with the versatility of cell engineering, OTR can serve as an “enabler” for TCR-based therapies. |
| first_indexed | 2024-03-10T19:27:18Z |
| format | Article |
| id | doaj.art-fc1505a8836d4a05a25c00bf46f19c32 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T19:27:18Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-fc1505a8836d4a05a25c00bf46f19c322023-11-20T02:28:55ZengMDPI AGCells2073-44092020-06-0196136710.3390/cells9061367Orthotopic T-Cell Receptor Replacement—An “Enabler” for TCR-Based TherapiesKilian Schober0Thomas R. Müller1Dirk H. Busch2Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), 81675 Munich, GermanyInstitute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), 81675 Munich, GermanyInstitute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), 81675 Munich, GermanyNatural adaptive immunity co-evolved with pathogens over millions of years, and adoptive transfer of non-engineered T cells to fight infections or cancer so far exhibits an exceptionally safe and functional therapeutic profile in clinical trials. However, the personalized nature of therapies using virus-specific T cells, donor lymphocyte infusion, or tumor-infiltrating lymphocytes makes implementation in routine clinical care difficult. In principle, genetic engineering can be used to make T-cell therapies more broadly applicable, but so far it significantly alters the physiology of cells. We recently demonstrated that orthotopic T-cell receptor (TCR) replacement (OTR) by clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR-associated protein 9 (Cas9) can be used to generate engineered T cells with preservation of near-physiological function. In this review, we present the current status of OTR technology development and discuss its potential for TCR-based therapies. By providing the means to combine the therapeutic efficacy and safety profile of physiological T cells with the versatility of cell engineering, OTR can serve as an “enabler” for TCR-based therapies.https://www.mdpi.com/2073-4409/9/6/1367TCR engineeringCRISPR/Cas9orthotopic TCR replacementOTRgene editingadoptive cell therapy |
| spellingShingle | Kilian Schober Thomas R. Müller Dirk H. Busch Orthotopic T-Cell Receptor Replacement—An “Enabler” for TCR-Based Therapies Cells TCR engineering CRISPR/Cas9 orthotopic TCR replacement OTR gene editing adoptive cell therapy |
| title | Orthotopic T-Cell Receptor Replacement—An “Enabler” for TCR-Based Therapies |
| title_full | Orthotopic T-Cell Receptor Replacement—An “Enabler” for TCR-Based Therapies |
| title_fullStr | Orthotopic T-Cell Receptor Replacement—An “Enabler” for TCR-Based Therapies |
| title_full_unstemmed | Orthotopic T-Cell Receptor Replacement—An “Enabler” for TCR-Based Therapies |
| title_short | Orthotopic T-Cell Receptor Replacement—An “Enabler” for TCR-Based Therapies |
| title_sort | orthotopic t cell receptor replacement an enabler for tcr based therapies |
| topic | TCR engineering CRISPR/Cas9 orthotopic TCR replacement OTR gene editing adoptive cell therapy |
| url | https://www.mdpi.com/2073-4409/9/6/1367 |
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