Article ; Online: CCR10-mediated Enhancement of T Cell Trafficking for Improved Tumor Immunotherapy.
2024 Volume 44, Issue 2, Page(s) 521–532
Abstract: Background/aim: The effectiveness of adoptive T cell therapy for solid tumors remains suboptimal, partly attributed to insufficient T cell infiltration into the tumor site. A promising strategy involves directing T cells towards the tumor utilizing ... ...
| Abstract | Background/aim: The effectiveness of adoptive T cell therapy for solid tumors remains suboptimal, partly attributed to insufficient T cell infiltration into the tumor site. A promising strategy involves directing T cells towards the tumor utilizing tumor-specific chemokine receptors. Materials and methods: We analyzed chemokine receptor expression in activated T cells and chemokine expression in breast and lung cancer using The Cancer Genome Atlas (TCGA) data. Subsequently, we generated 1G4 T cell receptor-engineered T (TCR-T) cells with CCR10 and performed in vitro and in vivo efficacy tests. Results: CCR10 exhibited insufficient expression in various human T cells. Analysis of TCGA RNA sequencing data revealed elevated expression of the chemokine CCL28, the corresponding chemokine for CCR10, in breast and lung cancer. Consequently, we generated CCR10-1G4 TCR-T cells. CCR10-1G4 dual expressing TCR-T cells exhibited comparable cellular cytotoxicity but increased mobility compared to 1G4 TCR-T cells in vitro. Furthermore, injecting CCR10-1G4 dual expressing TCR-T cells into a xenograft tumor model demonstrated enhanced in vivo trafficking and a greater reduction of tumor burden. Conclusion: This study highlights the potential of CCR10 for developing efficient adoptive T-cell treatments targeting solid tumors. |
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| MeSH term(s) | Humans ; T-Lymphocytes/metabolism ; Chemokines/metabolism ; Receptors, Chemokine ; Immunotherapy ; Lung Neoplasms/therapy ; Receptors, Antigen, T-Cell/genetics ; Receptors, CCR10/genetics ; Receptors, CCR10/metabolism |
| Chemical Substances | Chemokines ; Receptors, Chemokine ; Receptors, Antigen, T-Cell ; CCR10 protein, human ; Receptors, CCR10 |
| Language | English |
| Publishing date | 2024-02-01 |
| Publishing country | Greece |
| Document type | Journal Article |
| ZDB-ID | 604549-2 |
| ISSN | 1791-7530 ; 0250-7005 |
| ISSN (online) | 1791-7530 |
| ISSN | 0250-7005 |
| DOI | 10.21873/anticanres.16840 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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