Expansion and characterization of human melanoma tumor-infiltrating lymphocytes (TILs).
<h4>Background</h4>Various immunotherapeutic strategies for cancer are aimed at augmenting the T cell response against tumor cells. Adoptive cell therapy (ACT), where T cells are manipulated ex vivo and subsequently re-infused in an autologous manner, has been performed using T cells fro...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2010
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/fd7e427dc12b40768de11d9f16cd9cac |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:fd7e427dc12b40768de11d9f16cd9cac |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:fd7e427dc12b40768de11d9f16cd9cac2021-11-18T07:36:59ZExpansion and characterization of human melanoma tumor-infiltrating lymphocytes (TILs).1932-620310.1371/journal.pone.0013940https://doaj.org/article/fd7e427dc12b40768de11d9f16cd9cac2010-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21085676/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Various immunotherapeutic strategies for cancer are aimed at augmenting the T cell response against tumor cells. Adoptive cell therapy (ACT), where T cells are manipulated ex vivo and subsequently re-infused in an autologous manner, has been performed using T cells from various sources. Some of the highest clinical response rates for metastatic melanoma have been reported in trials using tumor-infiltrating lymphocytes (TILs). These protocols still have room for improvement and furthermore are currently only performed at a limited number of institutions. The goal of this work was to develop TILs as a therapeutic product at our institution.<h4>Principal findings</h4>TILs from 40 melanoma tissue specimens were expanded and characterized. Under optimized culture conditions, 72% of specimens yielded rapidly proliferating TILs as defined as at least one culture reaching ≥3×10(7) TILs within 4 weeks. Flow cytometric analyses showed that cultures were predominantly CD3+ T cells, with highly variable CD4+:CD8+ T cell ratios. In total, 148 independent bulk TIL cultures were assayed for tumor reactivity. Thirty-four percent (50/148) exhibited tumor reactivity based on IFN-γ production and/or cytotoxic activity. Thirteen percent (19/148) showed specific cytotoxic activity but not IFN-γ production and only 1% (2/148) showed specific IFN-γ production but not cytotoxic activity. Further expansion of TILs using a 14-day "rapid expansion protocol" (REP) is required to induce a 500- to 2000-fold expansion of TILs in order to generate sufficient numbers of cells for current ACT protocols. Thirty-eight consecutive test REPs were performed with an average 1865-fold expansion (+/- 1034-fold) after 14 days.<h4>Conclusions</h4>TILs generally expanded efficiently and tumor reactivity could be detected in vitro. These preclinical data from melanoma TILs lay the groundwork for clinical trials of ACT.Linh T NguyenPei Hua YenJessica NieNicole LiadisDanny GhazarianAyman Al-HabeebAlexandra EassonWey LeongJoan LipaDavid McCreadyMichael ReedijkDavid HoggAnthony M JoshuaIan QuirtHans MessnerPatricia ShawMichael CrumpEran SharonPamela S OhashiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 11, p e13940 (2010) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Linh T Nguyen Pei Hua Yen Jessica Nie Nicole Liadis Danny Ghazarian Ayman Al-Habeeb Alexandra Easson Wey Leong Joan Lipa David McCready Michael Reedijk David Hogg Anthony M Joshua Ian Quirt Hans Messner Patricia Shaw Michael Crump Eran Sharon Pamela S Ohashi Expansion and characterization of human melanoma tumor-infiltrating lymphocytes (TILs). |
| description |
<h4>Background</h4>Various immunotherapeutic strategies for cancer are aimed at augmenting the T cell response against tumor cells. Adoptive cell therapy (ACT), where T cells are manipulated ex vivo and subsequently re-infused in an autologous manner, has been performed using T cells from various sources. Some of the highest clinical response rates for metastatic melanoma have been reported in trials using tumor-infiltrating lymphocytes (TILs). These protocols still have room for improvement and furthermore are currently only performed at a limited number of institutions. The goal of this work was to develop TILs as a therapeutic product at our institution.<h4>Principal findings</h4>TILs from 40 melanoma tissue specimens were expanded and characterized. Under optimized culture conditions, 72% of specimens yielded rapidly proliferating TILs as defined as at least one culture reaching ≥3×10(7) TILs within 4 weeks. Flow cytometric analyses showed that cultures were predominantly CD3+ T cells, with highly variable CD4+:CD8+ T cell ratios. In total, 148 independent bulk TIL cultures were assayed for tumor reactivity. Thirty-four percent (50/148) exhibited tumor reactivity based on IFN-γ production and/or cytotoxic activity. Thirteen percent (19/148) showed specific cytotoxic activity but not IFN-γ production and only 1% (2/148) showed specific IFN-γ production but not cytotoxic activity. Further expansion of TILs using a 14-day "rapid expansion protocol" (REP) is required to induce a 500- to 2000-fold expansion of TILs in order to generate sufficient numbers of cells for current ACT protocols. Thirty-eight consecutive test REPs were performed with an average 1865-fold expansion (+/- 1034-fold) after 14 days.<h4>Conclusions</h4>TILs generally expanded efficiently and tumor reactivity could be detected in vitro. These preclinical data from melanoma TILs lay the groundwork for clinical trials of ACT. |
| format |
article |
| author |
Linh T Nguyen Pei Hua Yen Jessica Nie Nicole Liadis Danny Ghazarian Ayman Al-Habeeb Alexandra Easson Wey Leong Joan Lipa David McCready Michael Reedijk David Hogg Anthony M Joshua Ian Quirt Hans Messner Patricia Shaw Michael Crump Eran Sharon Pamela S Ohashi |
| author_facet |
Linh T Nguyen Pei Hua Yen Jessica Nie Nicole Liadis Danny Ghazarian Ayman Al-Habeeb Alexandra Easson Wey Leong Joan Lipa David McCready Michael Reedijk David Hogg Anthony M Joshua Ian Quirt Hans Messner Patricia Shaw Michael Crump Eran Sharon Pamela S Ohashi |
| author_sort |
Linh T Nguyen |
| title |
Expansion and characterization of human melanoma tumor-infiltrating lymphocytes (TILs). |
| title_short |
Expansion and characterization of human melanoma tumor-infiltrating lymphocytes (TILs). |
| title_full |
Expansion and characterization of human melanoma tumor-infiltrating lymphocytes (TILs). |
| title_fullStr |
Expansion and characterization of human melanoma tumor-infiltrating lymphocytes (TILs). |
| title_full_unstemmed |
Expansion and characterization of human melanoma tumor-infiltrating lymphocytes (TILs). |
| title_sort |
expansion and characterization of human melanoma tumor-infiltrating lymphocytes (tils). |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/fd7e427dc12b40768de11d9f16cd9cac |
| work_keys_str_mv |
AT linhtnguyen expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils AT peihuayen expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils AT jessicanie expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils AT nicoleliadis expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils AT dannyghazarian expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils AT aymanalhabeeb expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils AT alexandraeasson expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils AT weyleong expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils AT joanlipa expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils AT davidmccready expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils AT michaelreedijk expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils AT davidhogg expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils AT anthonymjoshua expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils AT ianquirt expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils AT hansmessner expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils AT patriciashaw expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils AT michaelcrump expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils AT eransharon expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils AT pamelasohashi expansionandcharacterizationofhumanmelanomatumorinfiltratinglymphocytestils |
| _version_ |
1718423200854966272 |