T-Cell Gene Therapy in Cancer Immunotherapy: Why It Is No Longer Just CARs on The Road
T-cells have a natural ability to fight cancer cells in the tumour microenvironment. Due to thymic selection and tissue-driven immunomodulation, these cancer-fighting T-cells are generally low in number and exhausted. One way to overcome these issues is to genetically alter T-cells to improve their...
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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/2073-4409/9/7/1588 |
| _version_ | 1797563631914713088 |
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| author | Michael D. Crowther Inge Marie Svane Özcan Met |
| author_facet | Michael D. Crowther Inge Marie Svane Özcan Met |
| author_sort | Michael D. Crowther |
| collection | DOAJ |
| description | T-cells have a natural ability to fight cancer cells in the tumour microenvironment. Due to thymic selection and tissue-driven immunomodulation, these cancer-fighting T-cells are generally low in number and exhausted. One way to overcome these issues is to genetically alter T-cells to improve their effectiveness. This process can involve introducing a receptor that has high affinity for a tumour antigen, with two promising candidates known as chimeric-antigen receptors (CARs), or T-cell receptors (TCRs) with high tumour specificity. This review focuses on the editing of immune cells to introduce such novel receptors to improve immune responses to cancer. These new receptors redirect T-cells innate killing abilities to the appropriate target on cancer cells. CARs are modified receptors that recognise whole proteins on the surface of cancer cells. They have been shown to be very effective in haematological malignancies but have limited documented efficacy in solid cancers. TCRs recognise internal antigens and therefore enable targeting of a much wider range of antigens. TCRs require major histocompatibility complex (MHC) restriction but novel TCRs may have broader antigen recognition. Moreover, there are multiple cell types which can be used as targets to improve the “off-the-shelf” capabilities of these genetic engineering methods. |
| first_indexed | 2024-03-10T18:46:15Z |
| format | Article |
| id | doaj.art-3b992bcdf95e407c936b8a266d2bdbad |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T18:46:15Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-3b992bcdf95e407c936b8a266d2bdbad2023-11-20T05:29:01ZengMDPI AGCells2073-44092020-06-0197158810.3390/cells9071588T-Cell Gene Therapy in Cancer Immunotherapy: Why It Is No Longer Just CARs on The RoadMichael D. Crowther0Inge Marie Svane1Özcan Met2Department of Oncology, National Center for Cancer Immune Therapy (CCIT-DK), Copenhagen University Hospital Herlev, 2730 Herlev, DenmarkDepartment of Oncology, National Center for Cancer Immune Therapy (CCIT-DK), Copenhagen University Hospital Herlev, 2730 Herlev, DenmarkDepartment of Oncology, National Center for Cancer Immune Therapy (CCIT-DK), Copenhagen University Hospital Herlev, 2730 Herlev, DenmarkT-cells have a natural ability to fight cancer cells in the tumour microenvironment. Due to thymic selection and tissue-driven immunomodulation, these cancer-fighting T-cells are generally low in number and exhausted. One way to overcome these issues is to genetically alter T-cells to improve their effectiveness. This process can involve introducing a receptor that has high affinity for a tumour antigen, with two promising candidates known as chimeric-antigen receptors (CARs), or T-cell receptors (TCRs) with high tumour specificity. This review focuses on the editing of immune cells to introduce such novel receptors to improve immune responses to cancer. These new receptors redirect T-cells innate killing abilities to the appropriate target on cancer cells. CARs are modified receptors that recognise whole proteins on the surface of cancer cells. They have been shown to be very effective in haematological malignancies but have limited documented efficacy in solid cancers. TCRs recognise internal antigens and therefore enable targeting of a much wider range of antigens. TCRs require major histocompatibility complex (MHC) restriction but novel TCRs may have broader antigen recognition. Moreover, there are multiple cell types which can be used as targets to improve the “off-the-shelf” capabilities of these genetic engineering methods.https://www.mdpi.com/2073-4409/9/7/1588CAR-TTCR-TT-cellscancerimmunotherapy |
| spellingShingle | Michael D. Crowther Inge Marie Svane Özcan Met T-Cell Gene Therapy in Cancer Immunotherapy: Why It Is No Longer Just CARs on The Road Cells CAR-T TCR-T T-cells cancer immunotherapy |
| title | T-Cell Gene Therapy in Cancer Immunotherapy: Why It Is No Longer Just CARs on The Road |
| title_full | T-Cell Gene Therapy in Cancer Immunotherapy: Why It Is No Longer Just CARs on The Road |
| title_fullStr | T-Cell Gene Therapy in Cancer Immunotherapy: Why It Is No Longer Just CARs on The Road |
| title_full_unstemmed | T-Cell Gene Therapy in Cancer Immunotherapy: Why It Is No Longer Just CARs on The Road |
| title_short | T-Cell Gene Therapy in Cancer Immunotherapy: Why It Is No Longer Just CARs on The Road |
| title_sort | t cell gene therapy in cancer immunotherapy why it is no longer just cars on the road |
| topic | CAR-T TCR-T T-cells cancer immunotherapy |
| url | https://www.mdpi.com/2073-4409/9/7/1588 |
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