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Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells
Peripheral T-cell lymphomas (PTCLs) are a group of very aggressive non-Hodgkin's lymphomas (NHLs) with poor prognoses and account for a majority of T-cell malignancies. Overall, the standard of care for patients with T-cell malignancies is poorly established, and there is an urgent clinical nee...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762550/ https://www.ncbi.nlm.nih.gov/pubmed/29348865 http://dx.doi.org/10.18632/oncotarget.22626 |
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author | Pinz, Kevin G. Yakaboski, Elizabeth Jares, Alexander Liu, Hua Firor, Amelia E. Chen, Kevin H. Wada, Masayuki Salman, Huda Tse, William Hagag, Nabil Lan, Fengshuo Leung, Elaine Lai-Han Jiang, Xun Ma, Yupo |
author_facet | Pinz, Kevin G. Yakaboski, Elizabeth Jares, Alexander Liu, Hua Firor, Amelia E. Chen, Kevin H. Wada, Masayuki Salman, Huda Tse, William Hagag, Nabil Lan, Fengshuo Leung, Elaine Lai-Han Jiang, Xun Ma, Yupo |
author_sort | Pinz, Kevin G. |
collection | PubMed |
description | Peripheral T-cell lymphomas (PTCLs) are a group of very aggressive non-Hodgkin's lymphomas (NHLs) with poor prognoses and account for a majority of T-cell malignancies. Overall, the standard of care for patients with T-cell malignancies is poorly established, and there is an urgent clinical need for a new approach. As demonstrated in B-cell malignancies, chimeric antigen receptor (CAR) immunotherapy provides great hope as a curative treatment regimen. Because PTCLs develop from mature T-cells, these NHLs are commonly CD4(+), and CD4 is highly and uniformly expressed. Therefore, CD4 is an ideal target for PTCL CAR immunotherapy. To that effect, we created a robust third-generation anti-CD4 CAR construct (CD4CAR) and introduced it into clonal NK cells (NK-92). CD4CAR NK-92 cells specifically and robustly eliminated diverse CD4(+) human T-cell leukemia and lymphoma cell lines (KARPAS-299, CCRF-CEM, and HL60) and patient samples ex vivo. Furthermore, CD4CAR NK-92 cells effectively targeted KARPAS-299 cells in vivo that modeled difficult-to-access lymphoma nodules, significantly prolonging survival. In our study, we present novel targeting of CD4 using CAR-modified NK cells, and demonstrate efficacy. Combined, our data support CD4CAR NK cell immunotherapy as a potential new avenue for the treatment of PTCLs and CD4(+) T-cell malignancies. |
format | Online Article Text |
id | pubmed-5762550 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-57625502018-01-18 Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells Pinz, Kevin G. Yakaboski, Elizabeth Jares, Alexander Liu, Hua Firor, Amelia E. Chen, Kevin H. Wada, Masayuki Salman, Huda Tse, William Hagag, Nabil Lan, Fengshuo Leung, Elaine Lai-Han Jiang, Xun Ma, Yupo Oncotarget Research Paper Peripheral T-cell lymphomas (PTCLs) are a group of very aggressive non-Hodgkin's lymphomas (NHLs) with poor prognoses and account for a majority of T-cell malignancies. Overall, the standard of care for patients with T-cell malignancies is poorly established, and there is an urgent clinical need for a new approach. As demonstrated in B-cell malignancies, chimeric antigen receptor (CAR) immunotherapy provides great hope as a curative treatment regimen. Because PTCLs develop from mature T-cells, these NHLs are commonly CD4(+), and CD4 is highly and uniformly expressed. Therefore, CD4 is an ideal target for PTCL CAR immunotherapy. To that effect, we created a robust third-generation anti-CD4 CAR construct (CD4CAR) and introduced it into clonal NK cells (NK-92). CD4CAR NK-92 cells specifically and robustly eliminated diverse CD4(+) human T-cell leukemia and lymphoma cell lines (KARPAS-299, CCRF-CEM, and HL60) and patient samples ex vivo. Furthermore, CD4CAR NK-92 cells effectively targeted KARPAS-299 cells in vivo that modeled difficult-to-access lymphoma nodules, significantly prolonging survival. In our study, we present novel targeting of CD4 using CAR-modified NK cells, and demonstrate efficacy. Combined, our data support CD4CAR NK cell immunotherapy as a potential new avenue for the treatment of PTCLs and CD4(+) T-cell malignancies. Impact Journals LLC 2017-11-22 /pmc/articles/PMC5762550/ /pubmed/29348865 http://dx.doi.org/10.18632/oncotarget.22626 Text en Copyright: © 2017 Pinz et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Pinz, Kevin G. Yakaboski, Elizabeth Jares, Alexander Liu, Hua Firor, Amelia E. Chen, Kevin H. Wada, Masayuki Salman, Huda Tse, William Hagag, Nabil Lan, Fengshuo Leung, Elaine Lai-Han Jiang, Xun Ma, Yupo Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells |
title | Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells |
title_full | Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells |
title_fullStr | Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells |
title_full_unstemmed | Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells |
title_short | Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells |
title_sort | targeting t-cell malignancies using anti-cd4 car nk-92 cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762550/ https://www.ncbi.nlm.nih.gov/pubmed/29348865 http://dx.doi.org/10.18632/oncotarget.22626 |
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