Long-lasting responses with chemotherapy followed by T-cell therapy in recurrent or metastatic EBV-related nasopharyngeal carcinoma
BackgroundRefractory or metastatic nasopharyngeal carcinoma (NPC) patients have a poor prognosis due to the lack of effective salvage treatments and prolonged survival by means of combination chemotherapy being described only for a minority of younger patients with oligometastatic disease. Targeting...
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1208475/full |
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| author | Simona Secondino Simona Secondino Paolo Pedrazzoli Paolo Pedrazzoli Paolo Pedrazzoli Sabrina Basso Sabrina Basso Paolo Bossi Alba Bianco Alba Bianco Ilaria Imarisio Ilaria Imarisio Anna Pagani Marica De Cicco Marica De Cicco Stella Muscianisi Stella Muscianisi Michela Casanova Carlo Morosi Cristiana Bergamini Marco Benazzo Marco Benazzo Maria Cossu Rocca Cesare Perotti Fausto Baldanti Fausto Baldanti Marco Zecca Lisa F. Licitra Lisa F. Licitra Patrizia Comoli Patrizia Comoli Patrizia Comoli |
| author_facet | Simona Secondino Simona Secondino Paolo Pedrazzoli Paolo Pedrazzoli Paolo Pedrazzoli Sabrina Basso Sabrina Basso Paolo Bossi Alba Bianco Alba Bianco Ilaria Imarisio Ilaria Imarisio Anna Pagani Marica De Cicco Marica De Cicco Stella Muscianisi Stella Muscianisi Michela Casanova Carlo Morosi Cristiana Bergamini Marco Benazzo Marco Benazzo Maria Cossu Rocca Cesare Perotti Fausto Baldanti Fausto Baldanti Marco Zecca Lisa F. Licitra Lisa F. Licitra Patrizia Comoli Patrizia Comoli Patrizia Comoli |
| author_sort | Simona Secondino |
| collection | DOAJ |
| description | BackgroundRefractory or metastatic nasopharyngeal carcinoma (NPC) patients have a poor prognosis due to the lack of effective salvage treatments and prolonged survival by means of combination chemotherapy being described only for a minority of younger patients with oligometastatic disease. Targeting the Epstein - Barr virus (EBV) proteins expressed in NPC cells has been shown to be a feasible strategy that could help control systemic disease.Patients and MethodsBetween 2011 and 2014, 16 patients with recurrent/metastatic EBV-NPC received first-line chemotherapy (CT) followed by 2 doses of autologous cytotoxic EBV specific T-lymphocytes (15-25 x 107 total cells/dose, 2 weeks apart), based on our previous studies showing the feasibility and efficacy of this infusion regimen. Cumulative overall survival (OS) and median OS were analysed in the whole population and according to specific clinical and biological parameters.ResultsAll patients received the planned T-cell therapy schedule, 9 after reaching partial (n=5) or complete (n=4) disease remission with CT, and 7 after failing to obtain benefit from chemotherapy. No severe adverse events were recorded. Patients who received cytotoxic T-lymphocytes (CTLs) had a cumulative 10-year OS of 44%, with a median OS of 60 months (95% CI 42-62). Patients responding to CT, with oligometastatic disease (<3 disease sites), and plasma EBV-DNA <1000 copies/mL had a better outcome.ConclusionsAutologous EBV-specific CTLs transplanted following conventional first-line CT demonstrated promising efficacy with several patients obtaining long-lasting disease control. The rationale provided by this study, with the crucial role likely played by the timing of CTL administration when trying to induce synergy with conventional treatment needs to be confirmed in a prospective controlled trial. |
| first_indexed | 2024-03-13T00:27:05Z |
| format | Article |
| id | doaj.art-70b97d3a68cf4cdeb949af93e505798c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T00:27:05Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-70b97d3a68cf4cdeb949af93e505798c2023-07-11T04:36:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-07-011410.3389/fimmu.2023.12084751208475Long-lasting responses with chemotherapy followed by T-cell therapy in recurrent or metastatic EBV-related nasopharyngeal carcinomaSimona Secondino0Simona Secondino1Paolo Pedrazzoli2Paolo Pedrazzoli3Paolo Pedrazzoli4Sabrina Basso5Sabrina Basso6Paolo Bossi7Alba Bianco8Alba Bianco9Ilaria Imarisio10Ilaria Imarisio11Anna Pagani12Marica De Cicco13Marica De Cicco14Stella Muscianisi15Stella Muscianisi16Michela Casanova17Carlo Morosi18Cristiana Bergamini19Marco Benazzo20Marco Benazzo21Maria Cossu Rocca22Cesare Perotti23Fausto Baldanti24Fausto Baldanti25Marco Zecca26Lisa F. Licitra27Lisa F. Licitra28Patrizia Comoli29Patrizia Comoli30Patrizia Comoli31Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, ItalyDepartment of Oncology, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, ItalyDepartment of Internal Medicine and Medical Therapy, University of Pavia, Pavia, ItalyDepartment of Oncology, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, ItalyCellular Therapy & Immunobiology Working Party, European Bone Marrow Transplantation (EBMT), Leiden, NetherlandsPediatric Hematology/Oncology, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, ItalyCell Factory, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, ItalyDepartment of Medical Oncology, University of Brescia-Azienda Socio-Sanitaria Territoriale (ASST) Spedali Civili, Brescia, ItalyPediatric Hematology/Oncology, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, ItalyCell Factory, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, ItalyDepartment of Internal Medicine and Medical Therapy, University of Pavia, Pavia, ItalyDepartment of Oncology, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, ItalyDepartment of Oncology, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, ItalyPediatric Hematology/Oncology, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, ItalyCell Factory, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, ItalyPediatric Hematology/Oncology, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, ItalyCell Factory, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, ItalyPediatric Oncology, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, ItalyRadiology Unit, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, ItalyHead and Neck Medical Oncology Unit, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, Italy0Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy1Otolaryngology - Head and Neck Surgery, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy2Department of Oncology, European Institute of Oncology (IEO) Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Milan, Italy3Immunohematology and Transfusion Service, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy0Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy4Microbiology and Molecular Virology Unit, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, ItalyPediatric Hematology/Oncology, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, ItalyHead and Neck Medical Oncology Unit, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milan, Italy5Department of Oncology and Hemato-Oncology, University of Milan, Milan, ItalyCellular Therapy & Immunobiology Working Party, European Bone Marrow Transplantation (EBMT), Leiden, NetherlandsPediatric Hematology/Oncology, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, ItalyCell Factory, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Policlinico S. Matteo, Pavia, ItalyBackgroundRefractory or metastatic nasopharyngeal carcinoma (NPC) patients have a poor prognosis due to the lack of effective salvage treatments and prolonged survival by means of combination chemotherapy being described only for a minority of younger patients with oligometastatic disease. Targeting the Epstein - Barr virus (EBV) proteins expressed in NPC cells has been shown to be a feasible strategy that could help control systemic disease.Patients and MethodsBetween 2011 and 2014, 16 patients with recurrent/metastatic EBV-NPC received first-line chemotherapy (CT) followed by 2 doses of autologous cytotoxic EBV specific T-lymphocytes (15-25 x 107 total cells/dose, 2 weeks apart), based on our previous studies showing the feasibility and efficacy of this infusion regimen. Cumulative overall survival (OS) and median OS were analysed in the whole population and according to specific clinical and biological parameters.ResultsAll patients received the planned T-cell therapy schedule, 9 after reaching partial (n=5) or complete (n=4) disease remission with CT, and 7 after failing to obtain benefit from chemotherapy. No severe adverse events were recorded. Patients who received cytotoxic T-lymphocytes (CTLs) had a cumulative 10-year OS of 44%, with a median OS of 60 months (95% CI 42-62). Patients responding to CT, with oligometastatic disease (<3 disease sites), and plasma EBV-DNA <1000 copies/mL had a better outcome.ConclusionsAutologous EBV-specific CTLs transplanted following conventional first-line CT demonstrated promising efficacy with several patients obtaining long-lasting disease control. The rationale provided by this study, with the crucial role likely played by the timing of CTL administration when trying to induce synergy with conventional treatment needs to be confirmed in a prospective controlled trial.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1208475/fullT-cell therapynasopharyngeal carcinomachemotherapyepstein-barr virusautologous cell transplant |
| spellingShingle | Simona Secondino Simona Secondino Paolo Pedrazzoli Paolo Pedrazzoli Paolo Pedrazzoli Sabrina Basso Sabrina Basso Paolo Bossi Alba Bianco Alba Bianco Ilaria Imarisio Ilaria Imarisio Anna Pagani Marica De Cicco Marica De Cicco Stella Muscianisi Stella Muscianisi Michela Casanova Carlo Morosi Cristiana Bergamini Marco Benazzo Marco Benazzo Maria Cossu Rocca Cesare Perotti Fausto Baldanti Fausto Baldanti Marco Zecca Lisa F. Licitra Lisa F. Licitra Patrizia Comoli Patrizia Comoli Patrizia Comoli Long-lasting responses with chemotherapy followed by T-cell therapy in recurrent or metastatic EBV-related nasopharyngeal carcinoma Frontiers in Immunology T-cell therapy nasopharyngeal carcinoma chemotherapy epstein-barr virus autologous cell transplant |
| title | Long-lasting responses with chemotherapy followed by T-cell therapy in recurrent or metastatic EBV-related nasopharyngeal carcinoma |
| title_full | Long-lasting responses with chemotherapy followed by T-cell therapy in recurrent or metastatic EBV-related nasopharyngeal carcinoma |
| title_fullStr | Long-lasting responses with chemotherapy followed by T-cell therapy in recurrent or metastatic EBV-related nasopharyngeal carcinoma |
| title_full_unstemmed | Long-lasting responses with chemotherapy followed by T-cell therapy in recurrent or metastatic EBV-related nasopharyngeal carcinoma |
| title_short | Long-lasting responses with chemotherapy followed by T-cell therapy in recurrent or metastatic EBV-related nasopharyngeal carcinoma |
| title_sort | long lasting responses with chemotherapy followed by t cell therapy in recurrent or metastatic ebv related nasopharyngeal carcinoma |
| topic | T-cell therapy nasopharyngeal carcinoma chemotherapy epstein-barr virus autologous cell transplant |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1208475/full |
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