NK cells specifically TCR-dressed to kill cancer cellsResearch in context
Background: Adoptive T-cell transfer of therapeutic TCR holds great promise to specifically kill cancer cells, but relies on modifying the patient's own T cells ex vivo before injection. The manufacturing of T cells in a tailor-made setting is a long and expensive process which could be resolve...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-02-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419300362 |
| _version_ | 1828474532264935424 |
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| author | Nadia Mensali Pierre Dillard Michael Hebeisen Susanne Lorenz Theodossis Theodossiou Marit Renée Myhre Anne Fåne Gustav Gaudernack Gunnar Kvalheim June Helen Myklebust Else Marit Inderberg Sébastien Wälchli |
| author_facet | Nadia Mensali Pierre Dillard Michael Hebeisen Susanne Lorenz Theodossis Theodossiou Marit Renée Myhre Anne Fåne Gustav Gaudernack Gunnar Kvalheim June Helen Myklebust Else Marit Inderberg Sébastien Wälchli |
| author_sort | Nadia Mensali |
| collection | DOAJ |
| description | Background: Adoptive T-cell transfer of therapeutic TCR holds great promise to specifically kill cancer cells, but relies on modifying the patient's own T cells ex vivo before injection. The manufacturing of T cells in a tailor-made setting is a long and expensive process which could be resolved by the use of universal cells. Currently, only the Natural Killer (NK) cell line NK-92 is FDA approved for universal use. In order to expand their recognition ability, they were equipped with Chimeric Antigen Receptors (CARs). However, unlike CARs, T-cell receptors (TCRs) can recognize all cellular proteins, which expand NK-92 recognition to the whole proteome. Methods: We herein genetically engineered NK-92 to express the CD3 signaling complex, and showed that it rendered them able to express a functional TCR. Functional assays and in vivo efficacy were used to validate these cells. Findings: This is the first demonstration that a non-T cell can exploit TCRs. This TCR-redirected cell line, termed TCR-NK-92, mimicked primary T cells phenotypically, metabolically and functionally, but retained its NK cell effector functions. Our results demonstrate a unique manner to indefinitely produce TCR-redirected lymphocytes at lower cost and with similar therapeutic efficacy as redirected T cells. Interpretation: These results suggest that an NK cell line could be the basis for an off-the-shelf TCR-based cancer immunotherapy solution. Fund: This work was supported by the Research Council of Norway (#254817), South-Eastern Norway Regional Health Authority (#14/00500-79), by OUS-Radiumhospitalet (Gene Therapy program) and the department of Oncology at the University of Lausanne. Keywords: Immunotherapy, TCR, T cell, Natural killer |
| first_indexed | 2024-12-11T06:01:04Z |
| format | Article |
| id | doaj.art-baa96d23750c455aa947c1f06061880a |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-11T06:01:04Z |
| publishDate | 2019-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-baa96d23750c455aa947c1f06061880a2022-12-22T01:18:28ZengElsevierEBioMedicine2352-39642019-02-0140106117NK cells specifically TCR-dressed to kill cancer cellsResearch in contextNadia Mensali0Pierre Dillard1Michael Hebeisen2Susanne Lorenz3Theodossis Theodossiou4Marit Renée Myhre5Anne Fåne6Gustav Gaudernack7Gunnar Kvalheim8June Helen Myklebust9Else Marit Inderberg10Sébastien Wälchli11Department of Cellular Therapy, Department for Cancer Therapy, Oslo University Hospital Radiumhospitalet, Oslo 0379, NorwayDepartment of Cellular Therapy, Department for Cancer Therapy, Oslo University Hospital Radiumhospitalet, Oslo 0379, NorwayCentre Universitaire Hospitalier Vaudois, University of Lausanne, Lausanne 1011, SwitzerlandDepartment of Core Facilities, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo 0379, NorwayDepartment of Radiation Biology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo 0379, NorwayDepartment of Cellular Therapy, Department for Cancer Therapy, Oslo University Hospital Radiumhospitalet, Oslo 0379, NorwayDepartment of Cellular Therapy, Department for Cancer Therapy, Oslo University Hospital Radiumhospitalet, Oslo 0379, NorwayDepartment of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo 0379, NorwayDepartment of Cellular Therapy, Department for Cancer Therapy, Oslo University Hospital Radiumhospitalet, Oslo 0379, NorwayDepartment of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo 0379, Norway; Centre for Cancer Biomedicine, University of Oslo, Oslo 0316, NorwayDepartment of Cellular Therapy, Department for Cancer Therapy, Oslo University Hospital Radiumhospitalet, Oslo 0379, Norway; Corresponding authors at: Department of Cellular Therapy, Oslo University Hospital Radiumhospitalet, Montebello, Oslo 0379, Norway.Department of Cellular Therapy, Department for Cancer Therapy, Oslo University Hospital Radiumhospitalet, Oslo 0379, Norway; Corresponding authors at: Department of Cellular Therapy, Oslo University Hospital Radiumhospitalet, Montebello, Oslo 0379, Norway.Background: Adoptive T-cell transfer of therapeutic TCR holds great promise to specifically kill cancer cells, but relies on modifying the patient's own T cells ex vivo before injection. The manufacturing of T cells in a tailor-made setting is a long and expensive process which could be resolved by the use of universal cells. Currently, only the Natural Killer (NK) cell line NK-92 is FDA approved for universal use. In order to expand their recognition ability, they were equipped with Chimeric Antigen Receptors (CARs). However, unlike CARs, T-cell receptors (TCRs) can recognize all cellular proteins, which expand NK-92 recognition to the whole proteome. Methods: We herein genetically engineered NK-92 to express the CD3 signaling complex, and showed that it rendered them able to express a functional TCR. Functional assays and in vivo efficacy were used to validate these cells. Findings: This is the first demonstration that a non-T cell can exploit TCRs. This TCR-redirected cell line, termed TCR-NK-92, mimicked primary T cells phenotypically, metabolically and functionally, but retained its NK cell effector functions. Our results demonstrate a unique manner to indefinitely produce TCR-redirected lymphocytes at lower cost and with similar therapeutic efficacy as redirected T cells. Interpretation: These results suggest that an NK cell line could be the basis for an off-the-shelf TCR-based cancer immunotherapy solution. Fund: This work was supported by the Research Council of Norway (#254817), South-Eastern Norway Regional Health Authority (#14/00500-79), by OUS-Radiumhospitalet (Gene Therapy program) and the department of Oncology at the University of Lausanne. Keywords: Immunotherapy, TCR, T cell, Natural killerhttp://www.sciencedirect.com/science/article/pii/S2352396419300362 |
| spellingShingle | Nadia Mensali Pierre Dillard Michael Hebeisen Susanne Lorenz Theodossis Theodossiou Marit Renée Myhre Anne Fåne Gustav Gaudernack Gunnar Kvalheim June Helen Myklebust Else Marit Inderberg Sébastien Wälchli NK cells specifically TCR-dressed to kill cancer cellsResearch in context EBioMedicine |
| title | NK cells specifically TCR-dressed to kill cancer cellsResearch in context |
| title_full | NK cells specifically TCR-dressed to kill cancer cellsResearch in context |
| title_fullStr | NK cells specifically TCR-dressed to kill cancer cellsResearch in context |
| title_full_unstemmed | NK cells specifically TCR-dressed to kill cancer cellsResearch in context |
| title_short | NK cells specifically TCR-dressed to kill cancer cellsResearch in context |
| title_sort | nk cells specifically tcr dressed to kill cancer cellsresearch in context |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419300362 |
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