SpCas9-expression by tumor cells can cause T cell-dependent tumor rejection in immunocompetent mice
The CRISPR/Cas9 system has recently emerged as a highly efficient modality in genetic engineering and has been widely considered for various therapeutic applications. However, since the effector protein, SpCas9, has a bacterial origin, its immunogenicity must be explored in further depth. Here, we f...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-05-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2019.1577127 |
| _version_ | 1818844286696816640 |
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| author | Reham Ajina Danielle Zamalin Annie Zuo Maha Moussa Marta Catalfamo Sandra A. Jablonski Louis M. Weiner |
| author_facet | Reham Ajina Danielle Zamalin Annie Zuo Maha Moussa Marta Catalfamo Sandra A. Jablonski Louis M. Weiner |
| author_sort | Reham Ajina |
| collection | DOAJ |
| description | The CRISPR/Cas9 system has recently emerged as a highly efficient modality in genetic engineering and has been widely considered for various therapeutic applications. However, since the effector protein, SpCas9, has a bacterial origin, its immunogenicity must be explored in further depth. Here, we found that the intact immune system, in wild-type C57BL/6J and BALB/cL mice, stimulates specific immune response against SpCas9, resulting in the rejection of SpCas9-expressing tumors. However, these tumors effectively grew in syngeneic C57BL/6J immunodeficient, T cell-depleted and Cas9-KI mice. Therefore, these observations suggest that this tumor rejection phenotype is T cell-dependent. The immunological clearance of SpCas9-expressing tumors in the immunocompetent group illustrates the possibility of misinterpreting the impact of CRISPR/Cas9-mediated gene editing on in vivo tumor biology and survival. Thus, these findings have important implications for the use of this exciting approach in in vivo studies, as well as to manipulate cancer cell biology for therapeutic applications. |
| first_indexed | 2024-12-19T05:11:21Z |
| format | Article |
| id | doaj.art-b09e8ff9467f4e9bb6896e116f04c68d |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-19T05:11:21Z |
| publishDate | 2019-05-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-b09e8ff9467f4e9bb6896e116f04c68d2022-12-21T20:34:47ZengTaylor & Francis GroupOncoImmunology2162-402X2019-05-018510.1080/2162402X.2019.15771271577127SpCas9-expression by tumor cells can cause T cell-dependent tumor rejection in immunocompetent miceReham Ajina0Danielle Zamalin1Annie Zuo2Maha Moussa3Marta Catalfamo4Sandra A. Jablonski5Louis M. Weiner6Georgetown University Medical CenterSchool of Nursing and Health Studies, Georgetown UniversityGeorgetown University Medical CenterGeorgetown University Medical CenterGeorgetown University Medical CenterGeorgetown University Medical CenterGeorgetown University Medical CenterThe CRISPR/Cas9 system has recently emerged as a highly efficient modality in genetic engineering and has been widely considered for various therapeutic applications. However, since the effector protein, SpCas9, has a bacterial origin, its immunogenicity must be explored in further depth. Here, we found that the intact immune system, in wild-type C57BL/6J and BALB/cL mice, stimulates specific immune response against SpCas9, resulting in the rejection of SpCas9-expressing tumors. However, these tumors effectively grew in syngeneic C57BL/6J immunodeficient, T cell-depleted and Cas9-KI mice. Therefore, these observations suggest that this tumor rejection phenotype is T cell-dependent. The immunological clearance of SpCas9-expressing tumors in the immunocompetent group illustrates the possibility of misinterpreting the impact of CRISPR/Cas9-mediated gene editing on in vivo tumor biology and survival. Thus, these findings have important implications for the use of this exciting approach in in vivo studies, as well as to manipulate cancer cell biology for therapeutic applications.http://dx.doi.org/10.1080/2162402X.2019.1577127crispr-cas9spcas9crisprimmunity |
| spellingShingle | Reham Ajina Danielle Zamalin Annie Zuo Maha Moussa Marta Catalfamo Sandra A. Jablonski Louis M. Weiner SpCas9-expression by tumor cells can cause T cell-dependent tumor rejection in immunocompetent mice OncoImmunology crispr-cas9 spcas9 crispr immunity |
| title | SpCas9-expression by tumor cells can cause T cell-dependent tumor rejection in immunocompetent mice |
| title_full | SpCas9-expression by tumor cells can cause T cell-dependent tumor rejection in immunocompetent mice |
| title_fullStr | SpCas9-expression by tumor cells can cause T cell-dependent tumor rejection in immunocompetent mice |
| title_full_unstemmed | SpCas9-expression by tumor cells can cause T cell-dependent tumor rejection in immunocompetent mice |
| title_short | SpCas9-expression by tumor cells can cause T cell-dependent tumor rejection in immunocompetent mice |
| title_sort | spcas9 expression by tumor cells can cause t cell dependent tumor rejection in immunocompetent mice |
| topic | crispr-cas9 spcas9 crispr immunity |
| url | http://dx.doi.org/10.1080/2162402X.2019.1577127 |
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