Cargando…
Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma
Autologous T cells transduced to express a high affinity T-cell receptor specific to NY-ESO-1 (letetresgene autoleucel, lete-cel) show promise in the treatment of metastatic synovial sarcoma, with 50% overall response rate. The efficacy of lete-cel treatment in 45 synovial sarcoma patients (NCT01343...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458750/ https://www.ncbi.nlm.nih.gov/pubmed/36075914 http://dx.doi.org/10.1038/s41467-022-32491-x |
_version_ | 1784786358201483264 |
---|---|
author | Gyurdieva, Alexandra Zajic, Stefan Chang, Ya-Fang Houseman, E. Andres Zhong, Shan Kim, Jaegil Nathenson, Michael Faitg, Thomas Woessner, Mary Turner, David C. Hasan, Aisha N. Glod, John Kaplan, Rosandra N. D’Angelo, Sandra P. Araujo, Dejka M. Chow, Warren A. Druta, Mihaela Demetri, George D. Van Tine, Brian A. Grupp, Stephan A. Fine, Gregg D. Eleftheriadou, Ioanna |
author_facet | Gyurdieva, Alexandra Zajic, Stefan Chang, Ya-Fang Houseman, E. Andres Zhong, Shan Kim, Jaegil Nathenson, Michael Faitg, Thomas Woessner, Mary Turner, David C. Hasan, Aisha N. Glod, John Kaplan, Rosandra N. D’Angelo, Sandra P. Araujo, Dejka M. Chow, Warren A. Druta, Mihaela Demetri, George D. Van Tine, Brian A. Grupp, Stephan A. Fine, Gregg D. Eleftheriadou, Ioanna |
author_sort | Gyurdieva, Alexandra |
collection | PubMed |
description | Autologous T cells transduced to express a high affinity T-cell receptor specific to NY-ESO-1 (letetresgene autoleucel, lete-cel) show promise in the treatment of metastatic synovial sarcoma, with 50% overall response rate. The efficacy of lete-cel treatment in 45 synovial sarcoma patients (NCT01343043) has been previously reported, however, biomarkers predictive of response and resistance remain to be better defined. This post-hoc analysis identifies associations of response to lete-cel with lymphodepleting chemotherapy regimen (LDR), product attributes, cell expansion, cytokines, and tumor gene expression. Responders have higher IL-15 levels pre-infusion (p = 0.011) and receive a higher number of transduced effector memory (CD45RA- CCR7-) CD8 + cells per kg (p = 0.039). Post-infusion, responders have increased IFNγ, IL-6, and peak cell expansion (p < 0.01, p < 0.01, and p = 0.016, respectively). Analysis of tumor samples post-treatment illustrates lete-cel infiltration and a decrease in expression of macrophage genes, suggesting remodeling of the tumor microenvironment. Here we report potential predictive and pharmacodynamic markers of lete-cel response that may inform LDR, cell dose, and strategies to enhance anticancer efficacy. |
format | Online Article Text |
id | pubmed-9458750 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-94587502022-09-10 Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma Gyurdieva, Alexandra Zajic, Stefan Chang, Ya-Fang Houseman, E. Andres Zhong, Shan Kim, Jaegil Nathenson, Michael Faitg, Thomas Woessner, Mary Turner, David C. Hasan, Aisha N. Glod, John Kaplan, Rosandra N. D’Angelo, Sandra P. Araujo, Dejka M. Chow, Warren A. Druta, Mihaela Demetri, George D. Van Tine, Brian A. Grupp, Stephan A. Fine, Gregg D. Eleftheriadou, Ioanna Nat Commun Article Autologous T cells transduced to express a high affinity T-cell receptor specific to NY-ESO-1 (letetresgene autoleucel, lete-cel) show promise in the treatment of metastatic synovial sarcoma, with 50% overall response rate. The efficacy of lete-cel treatment in 45 synovial sarcoma patients (NCT01343043) has been previously reported, however, biomarkers predictive of response and resistance remain to be better defined. This post-hoc analysis identifies associations of response to lete-cel with lymphodepleting chemotherapy regimen (LDR), product attributes, cell expansion, cytokines, and tumor gene expression. Responders have higher IL-15 levels pre-infusion (p = 0.011) and receive a higher number of transduced effector memory (CD45RA- CCR7-) CD8 + cells per kg (p = 0.039). Post-infusion, responders have increased IFNγ, IL-6, and peak cell expansion (p < 0.01, p < 0.01, and p = 0.016, respectively). Analysis of tumor samples post-treatment illustrates lete-cel infiltration and a decrease in expression of macrophage genes, suggesting remodeling of the tumor microenvironment. Here we report potential predictive and pharmacodynamic markers of lete-cel response that may inform LDR, cell dose, and strategies to enhance anticancer efficacy. Nature Publishing Group UK 2022-09-08 /pmc/articles/PMC9458750/ /pubmed/36075914 http://dx.doi.org/10.1038/s41467-022-32491-x Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Gyurdieva, Alexandra Zajic, Stefan Chang, Ya-Fang Houseman, E. Andres Zhong, Shan Kim, Jaegil Nathenson, Michael Faitg, Thomas Woessner, Mary Turner, David C. Hasan, Aisha N. Glod, John Kaplan, Rosandra N. D’Angelo, Sandra P. Araujo, Dejka M. Chow, Warren A. Druta, Mihaela Demetri, George D. Van Tine, Brian A. Grupp, Stephan A. Fine, Gregg D. Eleftheriadou, Ioanna Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma |
title | Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma |
title_full | Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma |
title_fullStr | Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma |
title_full_unstemmed | Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma |
title_short | Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma |
title_sort | biomarker correlates with response to ny-eso-1 tcr t cells in patients with synovial sarcoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9458750/ https://www.ncbi.nlm.nih.gov/pubmed/36075914 http://dx.doi.org/10.1038/s41467-022-32491-x |
work_keys_str_mv | AT gyurdievaalexandra biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT zajicstefan biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT changyafang biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT housemaneandres biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT zhongshan biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT kimjaegil biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT nathensonmichael biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT faitgthomas biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT woessnermary biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT turnerdavidc biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT hasanaishan biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT glodjohn biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT kaplanrosandran biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT dangelosandrap biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT araujodejkam biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT chowwarrena biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT drutamihaela biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT demetrigeorged biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT vantinebriana biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT gruppstephana biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT finegreggd biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma AT eleftheriadouioanna biomarkercorrelateswithresponsetonyeso1tcrtcellsinpatientswithsynovialsarcoma |