CRISPR/Cas9-based genome editing in the era of CAR T cell immunotherapy
The advent of engineered T cells as a form of immunotherapy marks the beginning of a new era in medicine, providing a transformative way to combat complex diseases such as cancer. Following FDA approval of CAR T cells directed against the CD19 protein for the treatment of acute lymphoblastic leukemi...
| 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: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21645515.2019.1571893 |
| _version_ | 1797677399257645056 |
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| author | January Salas-Mckee Weimin Kong Whitney L. Gladney Julie K. Jadlowsky Gabriela Plesa Megan M. Davis Joseph A. Fraietta |
| author_facet | January Salas-Mckee Weimin Kong Whitney L. Gladney Julie K. Jadlowsky Gabriela Plesa Megan M. Davis Joseph A. Fraietta |
| author_sort | January Salas-Mckee |
| collection | DOAJ |
| description | The advent of engineered T cells as a form of immunotherapy marks the beginning of a new era in medicine, providing a transformative way to combat complex diseases such as cancer. Following FDA approval of CAR T cells directed against the CD19 protein for the treatment of acute lymphoblastic leukemia and diffuse large B cell lymphoma, CAR T cells are poised to enter mainstream oncology. Despite this success, a number of patients are unable to receive this therapy due to inadequate T cell numbers or rapid disease progression. Furthermore, lack of response to CAR T cell treatment is due in some cases to intrinsic autologous T cell defects and/or the inability of these cells to function optimally in a strongly immunosuppressive tumor microenvironment. We describe recent efforts to overcome these limitations using CRISPR/Cas9 technology, with the goal of enhancing potency and increasing the availability of CAR-based therapies. We further discuss issues related to the efficiency/scalability of CRISPR/Cas9-mediated genome editing in CAR T cells and safety considerations. By combining the tools of synthetic biology such as CARs and CRISPR/Cas9, we have an unprecedented opportunity to optimally program T cells and improve adoptive immunotherapy for most, if not all future patients. |
| first_indexed | 2024-03-11T22:44:39Z |
| format | Article |
| id | doaj.art-41779d55186148e384de8c0f5be181d0 |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T22:44:39Z |
| publishDate | 2019-05-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-41779d55186148e384de8c0f5be181d02023-09-22T08:38:26ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2019-05-011551126113210.1080/21645515.2019.15718931571893CRISPR/Cas9-based genome editing in the era of CAR T cell immunotherapyJanuary Salas-Mckee0Weimin Kong1Whitney L. Gladney2Julie K. Jadlowsky3Gabriela Plesa4Megan M. Davis5Joseph A. Fraietta6University of PennsylvaniaUniversity of PennsylvaniaUniversity of PennsylvaniaUniversity of PennsylvaniaUniversity of PennsylvaniaUniversity of PennsylvaniaUniversity of PennsylvaniaThe advent of engineered T cells as a form of immunotherapy marks the beginning of a new era in medicine, providing a transformative way to combat complex diseases such as cancer. Following FDA approval of CAR T cells directed against the CD19 protein for the treatment of acute lymphoblastic leukemia and diffuse large B cell lymphoma, CAR T cells are poised to enter mainstream oncology. Despite this success, a number of patients are unable to receive this therapy due to inadequate T cell numbers or rapid disease progression. Furthermore, lack of response to CAR T cell treatment is due in some cases to intrinsic autologous T cell defects and/or the inability of these cells to function optimally in a strongly immunosuppressive tumor microenvironment. We describe recent efforts to overcome these limitations using CRISPR/Cas9 technology, with the goal of enhancing potency and increasing the availability of CAR-based therapies. We further discuss issues related to the efficiency/scalability of CRISPR/Cas9-mediated genome editing in CAR T cells and safety considerations. By combining the tools of synthetic biology such as CARs and CRISPR/Cas9, we have an unprecedented opportunity to optimally program T cells and improve adoptive immunotherapy for most, if not all future patients.http://dx.doi.org/10.1080/21645515.2019.1571893car t cellcrispr/cas9cancer immunotherapygenome editing |
| spellingShingle | January Salas-Mckee Weimin Kong Whitney L. Gladney Julie K. Jadlowsky Gabriela Plesa Megan M. Davis Joseph A. Fraietta CRISPR/Cas9-based genome editing in the era of CAR T cell immunotherapy Human Vaccines & Immunotherapeutics car t cell crispr/cas9 cancer immunotherapy genome editing |
| title | CRISPR/Cas9-based genome editing in the era of CAR T cell immunotherapy |
| title_full | CRISPR/Cas9-based genome editing in the era of CAR T cell immunotherapy |
| title_fullStr | CRISPR/Cas9-based genome editing in the era of CAR T cell immunotherapy |
| title_full_unstemmed | CRISPR/Cas9-based genome editing in the era of CAR T cell immunotherapy |
| title_short | CRISPR/Cas9-based genome editing in the era of CAR T cell immunotherapy |
| title_sort | crispr cas9 based genome editing in the era of car t cell immunotherapy |
| topic | car t cell crispr/cas9 cancer immunotherapy genome editing |
| url | http://dx.doi.org/10.1080/21645515.2019.1571893 |
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