Gene editing technology to improve antitumor T-cell functions in adoptive immunotherapy
Abstract Adoptive immunotherapy, in which tumor-reactive T cells are prepared in vitro for adoptive transfer to the patient, can induce an objective clinical response in specific types of cancer. In particular, chimeric antigen receptor (CAR)-redirected T-cell therapy has shown robust responses in h...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-03-01
|
| Series: | Inflammation and Regeneration |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s41232-024-00324-7 |
| _version_ | 1797259445531574272 |
|---|---|
| author | Yusuke Ito Satoshi Inoue Yuki Kagoya |
| author_facet | Yusuke Ito Satoshi Inoue Yuki Kagoya |
| author_sort | Yusuke Ito |
| collection | DOAJ |
| description | Abstract Adoptive immunotherapy, in which tumor-reactive T cells are prepared in vitro for adoptive transfer to the patient, can induce an objective clinical response in specific types of cancer. In particular, chimeric antigen receptor (CAR)-redirected T-cell therapy has shown robust responses in hematologic malignancies. However, its efficacy against most of the other tumors is still insufficient, which remains an unmet medical need. Accumulating evidence suggests that modifying specific genes can enhance antitumor T-cell properties. Epigenetic factors have been particularly implicated in the remodeling of T-cell functions, including changes to dysfunctional states such as terminal differentiation and exhaustion. Genetic ablation of key epigenetic molecules prevents the dysfunctional reprogramming of T cells and preserves their functional properties. Clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)-based gene editing is a valuable tool to enable efficient and specific gene editing in cultured T cells. A number of studies have already identified promising targets to improve the therapeutic efficacy of CAR-T cells using genome-wide or focused CRISPR screening. In this review, we will present recent representative findings on molecular insights into T-cell dysfunction and how genetic modification contributes to overcoming it. We will also discuss several technical advances to achieve efficient gene modification using the CRISPR and other novel platforms. |
| first_indexed | 2024-04-24T23:09:33Z |
| format | Article |
| id | doaj.art-a76d4c3cc4c54db79d1df4db972e596e |
| institution | Directory Open Access Journal |
| issn | 1880-8190 |
| language | English |
| last_indexed | 2024-04-24T23:09:33Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Inflammation and Regeneration |
| spelling | doaj.art-a76d4c3cc4c54db79d1df4db972e596e2024-03-17T12:18:24ZengBMCInflammation and Regeneration1880-81902024-03-0144111010.1186/s41232-024-00324-7Gene editing technology to improve antitumor T-cell functions in adoptive immunotherapyYusuke Ito0Satoshi Inoue1Yuki Kagoya2Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of MedicineDivision of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of MedicineDivision of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of MedicineAbstract Adoptive immunotherapy, in which tumor-reactive T cells are prepared in vitro for adoptive transfer to the patient, can induce an objective clinical response in specific types of cancer. In particular, chimeric antigen receptor (CAR)-redirected T-cell therapy has shown robust responses in hematologic malignancies. However, its efficacy against most of the other tumors is still insufficient, which remains an unmet medical need. Accumulating evidence suggests that modifying specific genes can enhance antitumor T-cell properties. Epigenetic factors have been particularly implicated in the remodeling of T-cell functions, including changes to dysfunctional states such as terminal differentiation and exhaustion. Genetic ablation of key epigenetic molecules prevents the dysfunctional reprogramming of T cells and preserves their functional properties. Clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)-based gene editing is a valuable tool to enable efficient and specific gene editing in cultured T cells. A number of studies have already identified promising targets to improve the therapeutic efficacy of CAR-T cells using genome-wide or focused CRISPR screening. In this review, we will present recent representative findings on molecular insights into T-cell dysfunction and how genetic modification contributes to overcoming it. We will also discuss several technical advances to achieve efficient gene modification using the CRISPR and other novel platforms.https://doi.org/10.1186/s41232-024-00324-7Adoptive immunotherapyChimeric antigen receptorEpigeneticsDNA methylationPRDM1Memory T cell |
| spellingShingle | Yusuke Ito Satoshi Inoue Yuki Kagoya Gene editing technology to improve antitumor T-cell functions in adoptive immunotherapy Inflammation and Regeneration Adoptive immunotherapy Chimeric antigen receptor Epigenetics DNA methylation PRDM1 Memory T cell |
| title | Gene editing technology to improve antitumor T-cell functions in adoptive immunotherapy |
| title_full | Gene editing technology to improve antitumor T-cell functions in adoptive immunotherapy |
| title_fullStr | Gene editing technology to improve antitumor T-cell functions in adoptive immunotherapy |
| title_full_unstemmed | Gene editing technology to improve antitumor T-cell functions in adoptive immunotherapy |
| title_short | Gene editing technology to improve antitumor T-cell functions in adoptive immunotherapy |
| title_sort | gene editing technology to improve antitumor t cell functions in adoptive immunotherapy |
| topic | Adoptive immunotherapy Chimeric antigen receptor Epigenetics DNA methylation PRDM1 Memory T cell |
| url | https://doi.org/10.1186/s41232-024-00324-7 |
| work_keys_str_mv | AT yusukeito geneeditingtechnologytoimproveantitumortcellfunctionsinadoptiveimmunotherapy AT satoshiinoue geneeditingtechnologytoimproveantitumortcellfunctionsinadoptiveimmunotherapy AT yukikagoya geneeditingtechnologytoimproveantitumortcellfunctionsinadoptiveimmunotherapy |