UniCAR T cell immunotherapy enables efficient elimination of radioresistant cancer cells
Induction or selection of radioresistant cancer (stem) cells following standard radiotherapy is presumably one of the major causes for recurrence of metastatic disease. One possibility to prevent tumor relapse is the application of targeted immunotherapies including, e.g., chimeric antigen receptor...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2020.1743036 |
| _version_ | 1818740439208951808 |
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| author | Claudia Arndt Liliana R. Loureiro Anja Feldmann Justyna Jureczek Ralf Bergmann Domokos Máthé Nikolett Hegedüs Nicole Berndt Stefanie Koristka Nicola Mitwasi Frederick Fasslrinner Chris Lamprecht Alexandra Kegler Anja Hoffmann Tabea Bartsch Ayşe Sedef Köseer Gary Egan Marc Schmitz Vaclav Hořejší Mechthild Krause Anna Dubrovska Michael Bachmann |
| author_facet | Claudia Arndt Liliana R. Loureiro Anja Feldmann Justyna Jureczek Ralf Bergmann Domokos Máthé Nikolett Hegedüs Nicole Berndt Stefanie Koristka Nicola Mitwasi Frederick Fasslrinner Chris Lamprecht Alexandra Kegler Anja Hoffmann Tabea Bartsch Ayşe Sedef Köseer Gary Egan Marc Schmitz Vaclav Hořejší Mechthild Krause Anna Dubrovska Michael Bachmann |
| author_sort | Claudia Arndt |
| collection | DOAJ |
| description | Induction or selection of radioresistant cancer (stem) cells following standard radiotherapy is presumably one of the major causes for recurrence of metastatic disease. One possibility to prevent tumor relapse is the application of targeted immunotherapies including, e.g., chimeric antigen receptor (CAR) T cells. In light of long-term remissions, it is highly relevant to clarify whether radioresistant cancer cells are susceptible to CAR T cell-mediated killing. To answer this question, we evaluated the anti-tumor activity of the switchable universal chimeric antigen receptor (UniCAR) system against highly radioresistant head and neck squamous cell carcinoma cells both in vitro and in vivo. Following specific UniCAR T cell engagement via EGFR or CD98 target modules, T cell effector mechanisms were induced including secretion of pro-inflammatory cytokines, up-regulation of granzyme B and perforin, as well as T cell proliferation. CD98- or EGFR-redirected UniCAR T cells further possess the capability to efficiently lyse radioresistant tumor cells. Observed anti-tumor effects were comparable to those against the radiosensitive parental cell lines. Finally, redirected UniCAR T cells significantly inhibited the growth of radioresistant cancer cells in immunodeficient mice. Taken together, our obtained data underline that the UniCAR system is able to overcome radioresistance. Thus, it represents an attractive technology for the development of combined radioimmunotherapeutic approaches that might improve the outcome of patients with metastatic radioresistant tumor diseases. |
| first_indexed | 2024-12-18T01:40:45Z |
| format | Article |
| id | doaj.art-e9bde3c3ab474cab96ef8a34e0e398cf |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-18T01:40:45Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-e9bde3c3ab474cab96ef8a34e0e398cf2022-12-21T21:25:20ZengTaylor & Francis GroupOncoImmunology2162-402X2020-01-019110.1080/2162402X.2020.17430361743036UniCAR T cell immunotherapy enables efficient elimination of radioresistant cancer cellsClaudia Arndt0Liliana R. Loureiro1Anja Feldmann2Justyna Jureczek3Ralf Bergmann4Domokos Máthé5Nikolett Hegedüs6Nicole Berndt7Stefanie Koristka8Nicola Mitwasi9Frederick Fasslrinner10Chris Lamprecht11Alexandra Kegler12Anja Hoffmann13Tabea Bartsch14Ayşe Sedef Köseer15Gary Egan16Marc Schmitz17Vaclav Hořejší18Mechthild Krause19Anna Dubrovska20Michael Bachmann21Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer ResearchHelmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer ResearchHelmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer ResearchGerman Cancer Consortium (DKTK), Partner Site Dresden and German Cancer Research Center (DKFZ)Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer ResearchSemmelweis UniversitySemmelweis UniversityHelmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer ResearchHelmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer ResearchHelmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer ResearchMedical Clinic and Polyclinic I, University Hospital Carl Gustav Carus, TU DresdenCenter of Clinical Neuroscience, University Hospital Carl Gustav Carus, TU DresdenHelmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer ResearchHelmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer ResearchHelmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer ResearchNational Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf (HZDR)Monash UniversityNational Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf (HZDR)Institute of Molecular Genetics of the Academy of Sciences of the Czech RepublicNational Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf (HZDR)National Center for Tumor Diseases (NCT), Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf (HZDR)Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer ResearchInduction or selection of radioresistant cancer (stem) cells following standard radiotherapy is presumably one of the major causes for recurrence of metastatic disease. One possibility to prevent tumor relapse is the application of targeted immunotherapies including, e.g., chimeric antigen receptor (CAR) T cells. In light of long-term remissions, it is highly relevant to clarify whether radioresistant cancer cells are susceptible to CAR T cell-mediated killing. To answer this question, we evaluated the anti-tumor activity of the switchable universal chimeric antigen receptor (UniCAR) system against highly radioresistant head and neck squamous cell carcinoma cells both in vitro and in vivo. Following specific UniCAR T cell engagement via EGFR or CD98 target modules, T cell effector mechanisms were induced including secretion of pro-inflammatory cytokines, up-regulation of granzyme B and perforin, as well as T cell proliferation. CD98- or EGFR-redirected UniCAR T cells further possess the capability to efficiently lyse radioresistant tumor cells. Observed anti-tumor effects were comparable to those against the radiosensitive parental cell lines. Finally, redirected UniCAR T cells significantly inhibited the growth of radioresistant cancer cells in immunodeficient mice. Taken together, our obtained data underline that the UniCAR system is able to overcome radioresistance. Thus, it represents an attractive technology for the development of combined radioimmunotherapeutic approaches that might improve the outcome of patients with metastatic radioresistant tumor diseases.http://dx.doi.org/10.1080/2162402X.2020.1743036radioresistancecd98egfradaptor cart cell immunotherapy |
| spellingShingle | Claudia Arndt Liliana R. Loureiro Anja Feldmann Justyna Jureczek Ralf Bergmann Domokos Máthé Nikolett Hegedüs Nicole Berndt Stefanie Koristka Nicola Mitwasi Frederick Fasslrinner Chris Lamprecht Alexandra Kegler Anja Hoffmann Tabea Bartsch Ayşe Sedef Köseer Gary Egan Marc Schmitz Vaclav Hořejší Mechthild Krause Anna Dubrovska Michael Bachmann UniCAR T cell immunotherapy enables efficient elimination of radioresistant cancer cells OncoImmunology radioresistance cd98 egfr adaptor car t cell immunotherapy |
| title | UniCAR T cell immunotherapy enables efficient elimination of radioresistant cancer cells |
| title_full | UniCAR T cell immunotherapy enables efficient elimination of radioresistant cancer cells |
| title_fullStr | UniCAR T cell immunotherapy enables efficient elimination of radioresistant cancer cells |
| title_full_unstemmed | UniCAR T cell immunotherapy enables efficient elimination of radioresistant cancer cells |
| title_short | UniCAR T cell immunotherapy enables efficient elimination of radioresistant cancer cells |
| title_sort | unicar t cell immunotherapy enables efficient elimination of radioresistant cancer cells |
| topic | radioresistance cd98 egfr adaptor car t cell immunotherapy |
| url | http://dx.doi.org/10.1080/2162402X.2020.1743036 |
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