Inducible de novo expression of neoantigens in tumor cells and mice
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Inducible expression of neoantigens in mice would enable the study of endogenous antigen-specific naïve T cell responses in disease and infection, but has been difficult to generate because leaky antigen expression in th...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Springer Science and Business Media LLC
2021
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| Online Access: | https://hdl.handle.net/1721.1/136073 |
| _version_ | 1811076347047444480 |
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| author | Damo, Martina Fitzgerald, Brittany Lu, Yisi Nader, Mursal William, Ivana Cheung, Julie F Connolly, Kelli A Foster, Gena G Akama-Garren, Elliot Lee, Da-Yae Chang, Greg P Gocheva, Vasilena Schmidt, Leah M Boileve, Alice Wilson, Josephine H Cui, Can Monroy, Isabel Gokare, Prashanth Cabeceiras, Peter Jacks, Tyler Joshi, Nikhil S |
| author_facet | Damo, Martina Fitzgerald, Brittany Lu, Yisi Nader, Mursal William, Ivana Cheung, Julie F Connolly, Kelli A Foster, Gena G Akama-Garren, Elliot Lee, Da-Yae Chang, Greg P Gocheva, Vasilena Schmidt, Leah M Boileve, Alice Wilson, Josephine H Cui, Can Monroy, Isabel Gokare, Prashanth Cabeceiras, Peter Jacks, Tyler Joshi, Nikhil S |
| author_sort | Damo, Martina |
| collection | MIT |
| description | © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Inducible expression of neoantigens in mice would enable the study of endogenous antigen-specific naïve T cell responses in disease and infection, but has been difficult to generate because leaky antigen expression in the thymus results in central T cell tolerance. Here we develop inversion-induced joined neoantigen (NINJA), using RNA splicing, DNA recombination and three levels of regulation to prevent leakiness and allow tight control over neoantigen expression. We apply NINJA to create tumor cell lines with inducible neoantigen expression, which could be used to study antitumor immunity. We also show that the genetic regulation in NINJA mice bypasses central and peripheral tolerance mechanisms and allows for robust endogenous CD8 and CD4 T cell responses on neoantigen induction in peripheral tissues. NINJA will enable studies of how T cells respond to defined neoantigens in the context of peripheral tolerance, transplantation, autoimmune diseases and cancer. |
| first_indexed | 2024-09-23T10:19:57Z |
| format | Article |
| id | mit-1721.1/136073 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:19:57Z |
| publishDate | 2021 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1360732021-10-28T04:31:53Z Inducible de novo expression of neoantigens in tumor cells and mice Damo, Martina Fitzgerald, Brittany Lu, Yisi Nader, Mursal William, Ivana Cheung, Julie F Connolly, Kelli A Foster, Gena G Akama-Garren, Elliot Lee, Da-Yae Chang, Greg P Gocheva, Vasilena Schmidt, Leah M Boileve, Alice Wilson, Josephine H Cui, Can Monroy, Isabel Gokare, Prashanth Cabeceiras, Peter Jacks, Tyler Joshi, Nikhil S © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Inducible expression of neoantigens in mice would enable the study of endogenous antigen-specific naïve T cell responses in disease and infection, but has been difficult to generate because leaky antigen expression in the thymus results in central T cell tolerance. Here we develop inversion-induced joined neoantigen (NINJA), using RNA splicing, DNA recombination and three levels of regulation to prevent leakiness and allow tight control over neoantigen expression. We apply NINJA to create tumor cell lines with inducible neoantigen expression, which could be used to study antitumor immunity. We also show that the genetic regulation in NINJA mice bypasses central and peripheral tolerance mechanisms and allows for robust endogenous CD8 and CD4 T cell responses on neoantigen induction in peripheral tissues. NINJA will enable studies of how T cells respond to defined neoantigens in the context of peripheral tolerance, transplantation, autoimmune diseases and cancer. 2021-10-27T20:30:40Z 2021-10-27T20:30:40Z 2021 2021-07-16T18:24:05Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136073 en 10.1038/S41587-020-0613-1 Nature Biotechnology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Springer Science and Business Media LLC PMC |
| spellingShingle | Damo, Martina Fitzgerald, Brittany Lu, Yisi Nader, Mursal William, Ivana Cheung, Julie F Connolly, Kelli A Foster, Gena G Akama-Garren, Elliot Lee, Da-Yae Chang, Greg P Gocheva, Vasilena Schmidt, Leah M Boileve, Alice Wilson, Josephine H Cui, Can Monroy, Isabel Gokare, Prashanth Cabeceiras, Peter Jacks, Tyler Joshi, Nikhil S Inducible de novo expression of neoantigens in tumor cells and mice |
| title | Inducible de novo expression of neoantigens in tumor cells and mice |
| title_full | Inducible de novo expression of neoantigens in tumor cells and mice |
| title_fullStr | Inducible de novo expression of neoantigens in tumor cells and mice |
| title_full_unstemmed | Inducible de novo expression of neoantigens in tumor cells and mice |
| title_short | Inducible de novo expression of neoantigens in tumor cells and mice |
| title_sort | inducible de novo expression of neoantigens in tumor cells and mice |
| url | https://hdl.handle.net/1721.1/136073 |
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