Unlocking the potential of allogeneic Vδ2 T cells for ovarian cancer therapy through CD16 biomarker selection and CAR/IL-15 engineering
Abstract Allogeneic Vγ9Vδ2 (Vδ2) T cells have emerged as attractive candidates for developing cancer therapy due to their established safety in allogeneic contexts and inherent tumor-fighting capabilities. Nonetheless, the limited clinical success of Vδ2 T cell-based treatments may be attributed to...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42619-2 |
| _version_ | 1797630134755262464 |
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| author | Derek Lee Zachary Spencer Dunn Wenbin Guo Carl J. Rosenthal Natalie E. Penn Yanqi Yu Kuangyi Zhou Zhe Li Feiyang Ma Miao Li Tsun-Ching Song Xinjian Cen Yan-Ruide Li Jin J. Zhou Matteo Pellegrini Pin Wang Lili Yang |
| author_facet | Derek Lee Zachary Spencer Dunn Wenbin Guo Carl J. Rosenthal Natalie E. Penn Yanqi Yu Kuangyi Zhou Zhe Li Feiyang Ma Miao Li Tsun-Ching Song Xinjian Cen Yan-Ruide Li Jin J. Zhou Matteo Pellegrini Pin Wang Lili Yang |
| author_sort | Derek Lee |
| collection | DOAJ |
| description | Abstract Allogeneic Vγ9Vδ2 (Vδ2) T cells have emerged as attractive candidates for developing cancer therapy due to their established safety in allogeneic contexts and inherent tumor-fighting capabilities. Nonetheless, the limited clinical success of Vδ2 T cell-based treatments may be attributed to donor variability, short-lived persistence, and tumor immune evasion. To address these constraints, we engineer Vδ2 T cells with enhanced attributes. By employing CD16 as a donor selection biomarker, we harness Vδ2 T cells characterized by heightened cytotoxicity and potent antibody-dependent cell-mediated cytotoxicity (ADCC) functionality. RNA sequencing analysis supports the augmented effector potential of Vδ2 T cells derived from CD16 high (CD16Hi) donors. Substantial enhancements are further achieved through CAR and IL-15 engineering methodologies. Preclinical investigations in two ovarian cancer models substantiate the effectiveness and safety of engineered CD16Hi Vδ2 T cells. These cells target tumors through multiple mechanisms, exhibit sustained in vivo persistence, and do not elicit graft-versus-host disease. These findings underscore the promise of engineered CD16Hi Vδ2 T cells as a viable therapeutic option for cancer treatment. |
| first_indexed | 2024-03-11T11:03:44Z |
| format | Article |
| id | doaj.art-db1b9f3012ed4c62863e57ef35407db7 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-11T11:03:44Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-db1b9f3012ed4c62863e57ef35407db72023-11-12T12:23:29ZengNature PortfolioNature Communications2041-17232023-11-0114111910.1038/s41467-023-42619-2Unlocking the potential of allogeneic Vδ2 T cells for ovarian cancer therapy through CD16 biomarker selection and CAR/IL-15 engineeringDerek Lee0Zachary Spencer Dunn1Wenbin Guo2Carl J. Rosenthal3Natalie E. Penn4Yanqi Yu5Kuangyi Zhou6Zhe Li7Feiyang Ma8Miao Li9Tsun-Ching Song10Xinjian Cen11Yan-Ruide Li12Jin J. Zhou13Matteo Pellegrini14Pin Wang15Lili Yang16Department of Microbiology, Immunology & Molecular Genetics, University of CaliforniaDepartment of Microbiology, Immunology & Molecular Genetics, University of CaliforniaBioinformatics Interdepartmental Program, University of CaliforniaDepartment of Microbiology, Immunology & Molecular Genetics, University of CaliforniaDepartment of Microbiology, Immunology & Molecular Genetics, University of CaliforniaDepartment of Microbiology, Immunology & Molecular Genetics, University of CaliforniaDepartment of Microbiology, Immunology & Molecular Genetics, University of CaliforniaDepartment of Microbiology, Immunology & Molecular Genetics, University of CaliforniaDepartment of Molecular, Cell, and Developmental Biology, University of CaliforniaDepartment of Microbiology, Immunology & Molecular Genetics, University of CaliforniaDepartment of Microbiology, Immunology & Molecular Genetics, University of CaliforniaDepartment of Microbiology, Immunology & Molecular Genetics, University of CaliforniaDepartment of Microbiology, Immunology & Molecular Genetics, University of CaliforniaDepartment of Biostatistics, Fielding School of Public Health, University of CaliforniaBioinformatics Interdepartmental Program, University of CaliforniaMork Family Department of Chemical Engineering and Materials Science, University of Southern CaliforniaDepartment of Microbiology, Immunology & Molecular Genetics, University of CaliforniaAbstract Allogeneic Vγ9Vδ2 (Vδ2) T cells have emerged as attractive candidates for developing cancer therapy due to their established safety in allogeneic contexts and inherent tumor-fighting capabilities. Nonetheless, the limited clinical success of Vδ2 T cell-based treatments may be attributed to donor variability, short-lived persistence, and tumor immune evasion. To address these constraints, we engineer Vδ2 T cells with enhanced attributes. By employing CD16 as a donor selection biomarker, we harness Vδ2 T cells characterized by heightened cytotoxicity and potent antibody-dependent cell-mediated cytotoxicity (ADCC) functionality. RNA sequencing analysis supports the augmented effector potential of Vδ2 T cells derived from CD16 high (CD16Hi) donors. Substantial enhancements are further achieved through CAR and IL-15 engineering methodologies. Preclinical investigations in two ovarian cancer models substantiate the effectiveness and safety of engineered CD16Hi Vδ2 T cells. These cells target tumors through multiple mechanisms, exhibit sustained in vivo persistence, and do not elicit graft-versus-host disease. These findings underscore the promise of engineered CD16Hi Vδ2 T cells as a viable therapeutic option for cancer treatment.https://doi.org/10.1038/s41467-023-42619-2 |
| spellingShingle | Derek Lee Zachary Spencer Dunn Wenbin Guo Carl J. Rosenthal Natalie E. Penn Yanqi Yu Kuangyi Zhou Zhe Li Feiyang Ma Miao Li Tsun-Ching Song Xinjian Cen Yan-Ruide Li Jin J. Zhou Matteo Pellegrini Pin Wang Lili Yang Unlocking the potential of allogeneic Vδ2 T cells for ovarian cancer therapy through CD16 biomarker selection and CAR/IL-15 engineering Nature Communications |
| title | Unlocking the potential of allogeneic Vδ2 T cells for ovarian cancer therapy through CD16 biomarker selection and CAR/IL-15 engineering |
| title_full | Unlocking the potential of allogeneic Vδ2 T cells for ovarian cancer therapy through CD16 biomarker selection and CAR/IL-15 engineering |
| title_fullStr | Unlocking the potential of allogeneic Vδ2 T cells for ovarian cancer therapy through CD16 biomarker selection and CAR/IL-15 engineering |
| title_full_unstemmed | Unlocking the potential of allogeneic Vδ2 T cells for ovarian cancer therapy through CD16 biomarker selection and CAR/IL-15 engineering |
| title_short | Unlocking the potential of allogeneic Vδ2 T cells for ovarian cancer therapy through CD16 biomarker selection and CAR/IL-15 engineering |
| title_sort | unlocking the potential of allogeneic vδ2 t cells for ovarian cancer therapy through cd16 biomarker selection and car il 15 engineering |
| url | https://doi.org/10.1038/s41467-023-42619-2 |
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