Three-dimensional dynamics of mesothelin-targeted CAR.CIK lymphocytes against ovarian cancer peritoneal carcinomatosis
Abstract Intraperitoneal cellular immunotherapy with CAR-redirected lymphocytes is an intriguing approach to target peritoneal carcinomatosis (PC) from ovarian cancer (OC), which is currently evaluated in clinical trials. PC displays a composite structure with floating tumor cells within ascites and...
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| Format: | Article |
| Language: | English |
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Springer
2024-11-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-024-03860-w |
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| author | Federica Galvagno Valeria Leuci Annamaria Massa Chiara Donini Ramona Rotolo Sonia Capellero Alessia Proment Letizia Vitali Andrea Maria Lombardi Valentina Tuninetti Lorenzo D’Ambrosio Alessandra Merlini Elisa Vigna Giorgio Valabrega Luca Primo Alberto Puliafito Dario Sangiolo |
| author_facet | Federica Galvagno Valeria Leuci Annamaria Massa Chiara Donini Ramona Rotolo Sonia Capellero Alessia Proment Letizia Vitali Andrea Maria Lombardi Valentina Tuninetti Lorenzo D’Ambrosio Alessandra Merlini Elisa Vigna Giorgio Valabrega Luca Primo Alberto Puliafito Dario Sangiolo |
| author_sort | Federica Galvagno |
| collection | DOAJ |
| description | Abstract Intraperitoneal cellular immunotherapy with CAR-redirected lymphocytes is an intriguing approach to target peritoneal carcinomatosis (PC) from ovarian cancer (OC), which is currently evaluated in clinical trials. PC displays a composite structure with floating tumor cells within ascites and solid-like masses invading the peritoneum. Therefore, a comprehensive experimental model is crucial to optimize CAR-cell therapies in such a peculiar environment. Here, we explored the activity of cytokine-induced killer lymphocytes (CIK), redirected by CAR against mesothelin (MSLN-CAR.CIK), within reductionistic 3D models resembling the structural complexity of both liquid and solid components of PC. MSLN-CAR.CIK effectively killed and were functionally efficient against OC targets. In a “floating-like” 3D context with floating OC spheroids, both tumor localization and killing by MSLN-CAR.CIK were significantly boosted by fluid flow. In a “solid-like” context, MSLN-CAR.CIK were recruited through the extracellular matrix on embedded tumor aggregates, with variable kinetics depending on the effector-target distance. Furthermore, MSLN-CAR.CIK penetrated the inner levels of OC spheroids exerting effective tumor killing. Our findings provide currently unknown therapeutically relevant information on intraperitoneal approaches with CAR.CIK, supporting further developments and improvements for clinical studies in the context of locoregional cell therapy approaches for patients with PC from OC. |
| format | Article |
| id | doaj-art-3f8296825a904b688902b192289d96ff |
| institution | Kabale University |
| issn | 1432-0851 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-3f8296825a904b688902b192289d96ff2025-02-02T12:26:36ZengSpringerCancer Immunology, Immunotherapy1432-08512024-11-0174111410.1007/s00262-024-03860-wThree-dimensional dynamics of mesothelin-targeted CAR.CIK lymphocytes against ovarian cancer peritoneal carcinomatosisFederica Galvagno0Valeria Leuci1Annamaria Massa2Chiara Donini3Ramona Rotolo4Sonia Capellero5Alessia Proment6Letizia Vitali7Andrea Maria Lombardi8Valentina Tuninetti9Lorenzo D’Ambrosio10Alessandra Merlini11Elisa Vigna12Giorgio Valabrega13Luca Primo14Alberto Puliafito15Dario Sangiolo16Department of Oncology, University of TorinoDepartment of Oncology, University of TorinoDepartment of Oncology, University of TorinoDepartment of Oncology, University of TorinoDepartment of Oncology, University of TorinoCandiolo Cancer Institute, FPO-IRCCSDepartment of Oncology, University of TorinoDepartment of Oncology, University of TorinoDepartment of Oncology, University of TorinoDepartment of Oncology, University of TorinoDepartment of Oncology, University of TorinoDepartment of Oncology, University of TorinoDepartment of Oncology, University of TorinoDepartment of Oncology, University of TorinoDepartment of Oncology, University of TorinoDepartment of Oncology, University of TorinoDepartment of Oncology, University of TorinoAbstract Intraperitoneal cellular immunotherapy with CAR-redirected lymphocytes is an intriguing approach to target peritoneal carcinomatosis (PC) from ovarian cancer (OC), which is currently evaluated in clinical trials. PC displays a composite structure with floating tumor cells within ascites and solid-like masses invading the peritoneum. Therefore, a comprehensive experimental model is crucial to optimize CAR-cell therapies in such a peculiar environment. Here, we explored the activity of cytokine-induced killer lymphocytes (CIK), redirected by CAR against mesothelin (MSLN-CAR.CIK), within reductionistic 3D models resembling the structural complexity of both liquid and solid components of PC. MSLN-CAR.CIK effectively killed and were functionally efficient against OC targets. In a “floating-like” 3D context with floating OC spheroids, both tumor localization and killing by MSLN-CAR.CIK were significantly boosted by fluid flow. In a “solid-like” context, MSLN-CAR.CIK were recruited through the extracellular matrix on embedded tumor aggregates, with variable kinetics depending on the effector-target distance. Furthermore, MSLN-CAR.CIK penetrated the inner levels of OC spheroids exerting effective tumor killing. Our findings provide currently unknown therapeutically relevant information on intraperitoneal approaches with CAR.CIK, supporting further developments and improvements for clinical studies in the context of locoregional cell therapy approaches for patients with PC from OC.https://doi.org/10.1007/s00262-024-03860-w3D modelsCellular immunotherapyChimeric antigen receptorOvarian cancerPeritoneal carcinomatosis |
| spellingShingle | Federica Galvagno Valeria Leuci Annamaria Massa Chiara Donini Ramona Rotolo Sonia Capellero Alessia Proment Letizia Vitali Andrea Maria Lombardi Valentina Tuninetti Lorenzo D’Ambrosio Alessandra Merlini Elisa Vigna Giorgio Valabrega Luca Primo Alberto Puliafito Dario Sangiolo Three-dimensional dynamics of mesothelin-targeted CAR.CIK lymphocytes against ovarian cancer peritoneal carcinomatosis Cancer Immunology, Immunotherapy 3D models Cellular immunotherapy Chimeric antigen receptor Ovarian cancer Peritoneal carcinomatosis |
| title | Three-dimensional dynamics of mesothelin-targeted CAR.CIK lymphocytes against ovarian cancer peritoneal carcinomatosis |
| title_full | Three-dimensional dynamics of mesothelin-targeted CAR.CIK lymphocytes against ovarian cancer peritoneal carcinomatosis |
| title_fullStr | Three-dimensional dynamics of mesothelin-targeted CAR.CIK lymphocytes against ovarian cancer peritoneal carcinomatosis |
| title_full_unstemmed | Three-dimensional dynamics of mesothelin-targeted CAR.CIK lymphocytes against ovarian cancer peritoneal carcinomatosis |
| title_short | Three-dimensional dynamics of mesothelin-targeted CAR.CIK lymphocytes against ovarian cancer peritoneal carcinomatosis |
| title_sort | three dimensional dynamics of mesothelin targeted car cik lymphocytes against ovarian cancer peritoneal carcinomatosis |
| topic | 3D models Cellular immunotherapy Chimeric antigen receptor Ovarian cancer Peritoneal carcinomatosis |
| url | https://doi.org/10.1007/s00262-024-03860-w |
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