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Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated With Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs
Extranodal NK/T-cell lymphoma (ENKTCL) is associated with latent Epstein-Barr virus (EBV) infection and frequent relapse even after complete response (CR) to intensive chemotherapy and radiotherapy. The expression of EBV proteins in the tumor provides targets for adoptive immunotherapy with antigen-...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817864/ https://www.ncbi.nlm.nih.gov/pubmed/26017177 http://dx.doi.org/10.1038/mt.2015.91 |
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author | Cho, Seok-Goo Kim, Nayoun Sohn, Hyun-Jung Lee, Suk Kyeong Oh, Sang Taek Lee, Hyun-Joo Cho, Hyun-Il Yim, Hyeon Woo Jung, Seung Eun Park, Gyeongsin Oh, Joo Hyun Choi, Byung-Ock Kim, Sung Won Kim, Soo Whan Chung, Nak Gyun Lee, Jong Wook Hong, Young Seon Kim, Tai-Gyu |
author_facet | Cho, Seok-Goo Kim, Nayoun Sohn, Hyun-Jung Lee, Suk Kyeong Oh, Sang Taek Lee, Hyun-Joo Cho, Hyun-Il Yim, Hyeon Woo Jung, Seung Eun Park, Gyeongsin Oh, Joo Hyun Choi, Byung-Ock Kim, Sung Won Kim, Soo Whan Chung, Nak Gyun Lee, Jong Wook Hong, Young Seon Kim, Tai-Gyu |
author_sort | Cho, Seok-Goo |
collection | PubMed |
description | Extranodal NK/T-cell lymphoma (ENKTCL) is associated with latent Epstein-Barr virus (EBV) infection and frequent relapse even after complete response (CR) to intensive chemotherapy and radiotherapy. The expression of EBV proteins in the tumor provides targets for adoptive immunotherapy with antigen-specific cytotoxic T cells (CTL). To evaluate the efficacy and safety of EBV latent membrane protein (LMP)-1 and LMP-2a-specific CTLs (LMP1/2a CTLs) stimulated with LMP1/2a RNA-transferred dendritic cells, we treated 10 ENKTCL patients who showed complete response to induction therapy. Patients who completed and responded to chemotherapy, radiotherapy, and/or high-dose therapy followed by stem cell transplantation (HDT/SCT) were eligible to receive eight doses of 2 × 10(7) LMP1/2a CTLs/m(2). Following infusion, there were no immediate or delayed toxicities. The 4-year overall survival (OS) and progression-free survival (PFS) were 100%, and 90% (95% CI: 71.4 to 100%) respectively with a median follow-up of 55·5 months. Circulating IFN-γ secreting LMP1 and LMP2a-specific T cells within the peripheral blood corresponded with decline in plasma EBV DNA levels in patients. Adoptive transfer of LMP1/2a CTLs in ENKTCL patients is a safe and effective postremission therapeutic approach. Further randomized studies will be needed to define the role of EBV-CTLs in preventing relapse of ENKTCL. |
format | Online Article Text |
id | pubmed-4817864 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48178642016-04-15 Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated With Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs Cho, Seok-Goo Kim, Nayoun Sohn, Hyun-Jung Lee, Suk Kyeong Oh, Sang Taek Lee, Hyun-Joo Cho, Hyun-Il Yim, Hyeon Woo Jung, Seung Eun Park, Gyeongsin Oh, Joo Hyun Choi, Byung-Ock Kim, Sung Won Kim, Soo Whan Chung, Nak Gyun Lee, Jong Wook Hong, Young Seon Kim, Tai-Gyu Mol Ther Original Article Extranodal NK/T-cell lymphoma (ENKTCL) is associated with latent Epstein-Barr virus (EBV) infection and frequent relapse even after complete response (CR) to intensive chemotherapy and radiotherapy. The expression of EBV proteins in the tumor provides targets for adoptive immunotherapy with antigen-specific cytotoxic T cells (CTL). To evaluate the efficacy and safety of EBV latent membrane protein (LMP)-1 and LMP-2a-specific CTLs (LMP1/2a CTLs) stimulated with LMP1/2a RNA-transferred dendritic cells, we treated 10 ENKTCL patients who showed complete response to induction therapy. Patients who completed and responded to chemotherapy, radiotherapy, and/or high-dose therapy followed by stem cell transplantation (HDT/SCT) were eligible to receive eight doses of 2 × 10(7) LMP1/2a CTLs/m(2). Following infusion, there were no immediate or delayed toxicities. The 4-year overall survival (OS) and progression-free survival (PFS) were 100%, and 90% (95% CI: 71.4 to 100%) respectively with a median follow-up of 55·5 months. Circulating IFN-γ secreting LMP1 and LMP2a-specific T cells within the peripheral blood corresponded with decline in plasma EBV DNA levels in patients. Adoptive transfer of LMP1/2a CTLs in ENKTCL patients is a safe and effective postremission therapeutic approach. Further randomized studies will be needed to define the role of EBV-CTLs in preventing relapse of ENKTCL. Nature Publishing Group 2015-08 2015-06-23 /pmc/articles/PMC4817864/ /pubmed/26017177 http://dx.doi.org/10.1038/mt.2015.91 Text en Copyright © 2015 American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Original Article Cho, Seok-Goo Kim, Nayoun Sohn, Hyun-Jung Lee, Suk Kyeong Oh, Sang Taek Lee, Hyun-Joo Cho, Hyun-Il Yim, Hyeon Woo Jung, Seung Eun Park, Gyeongsin Oh, Joo Hyun Choi, Byung-Ock Kim, Sung Won Kim, Soo Whan Chung, Nak Gyun Lee, Jong Wook Hong, Young Seon Kim, Tai-Gyu Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated With Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs |
title | Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated With Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs |
title_full | Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated With Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs |
title_fullStr | Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated With Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs |
title_full_unstemmed | Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated With Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs |
title_short | Long-term Outcome of Extranodal NK/T Cell Lymphoma Patients Treated With Postremission Therapy Using EBV LMP1 and LMP2a-specific CTLs |
title_sort | long-term outcome of extranodal nk/t cell lymphoma patients treated with postremission therapy using ebv lmp1 and lmp2a-specific ctls |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817864/ https://www.ncbi.nlm.nih.gov/pubmed/26017177 http://dx.doi.org/10.1038/mt.2015.91 |
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