Adoptive Transfer of Photosensitizer-Loaded Cytotoxic T Cells for Combinational Photodynamic Therapy and Cancer Immuno-Therapy
Adoptive cell transfer (ACT) has shown remarkable therapeutic efficacy against blood cancers such as leukemia and lymphomas, but its effect is still limited due to the lack of well-defined antigens expressed by aberrant cells within tumors, the insufficient trafficking of administered T cells to the...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2023-04-01
|
Series: | Pharmaceutics |
Subjects: | |
Online Access: | https://www.mdpi.com/1999-4923/15/4/1295 |
_version_ | 1797603778010021888 |
---|---|
author | André-René Blaudszun Woo Jun Kim Wooram Um Hong Yeol Yoon Man Kyu Shim Kwangmeyung Kim |
author_facet | André-René Blaudszun Woo Jun Kim Wooram Um Hong Yeol Yoon Man Kyu Shim Kwangmeyung Kim |
author_sort | André-René Blaudszun |
collection | DOAJ |
description | Adoptive cell transfer (ACT) has shown remarkable therapeutic efficacy against blood cancers such as leukemia and lymphomas, but its effect is still limited due to the lack of well-defined antigens expressed by aberrant cells within tumors, the insufficient trafficking of administered T cells to the tumor sites, as well as immunosuppression induced by the tumor microenvironment (TME). In this study, we propose the adoptive transfer of photosensitizer (PS)-loaded cytotoxic T cells for a combinational photodynamic and cancer immunotherapy. Temoporfin (Foscan<sup>®</sup>), a clinically applicable porphyrin derivative, was loaded into OT-1 cells (PS-OT-1 cells). The PS-OT-1 cells efficiently produced a large amount of reactive oxygen species (ROS) under visible light irradiation in a culture; importantly, the combinational photodynamic therapy (PDT) and ACT with PS-OT-1 cells induced significant cytotoxicity compared to ACT alone with unloaded OT-1 cells. In murine lymphoma models, intravenously injected PS-OT-1 cells significantly inhibited tumor growth compared to unloaded OT-1 cells when the tumor tissues were locally irradiated with visible light. Collectively, this study suggests that combinational PDT and ACT mediated by PS-OT-1 cells provides a new approach for effective cancer immunotherapy. |
first_indexed | 2024-03-11T04:36:54Z |
format | Article |
id | doaj.art-0401cb5dc0954e219dd8cd32586fea61 |
institution | Directory Open Access Journal |
issn | 1999-4923 |
language | English |
last_indexed | 2024-03-11T04:36:54Z |
publishDate | 2023-04-01 |
publisher | MDPI AG |
record_format | Article |
series | Pharmaceutics |
spelling | doaj.art-0401cb5dc0954e219dd8cd32586fea612023-11-17T20:55:28ZengMDPI AGPharmaceutics1999-49232023-04-01154129510.3390/pharmaceutics15041295Adoptive Transfer of Photosensitizer-Loaded Cytotoxic T Cells for Combinational Photodynamic Therapy and Cancer Immuno-TherapyAndré-René Blaudszun0Woo Jun Kim1Wooram Um2Hong Yeol Yoon3Man Kyu Shim4Kwangmeyung Kim5Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of KoreaMedicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of KoreaMedicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of KoreaMedicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of KoreaMedicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of KoreaCollege of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of KoreaAdoptive cell transfer (ACT) has shown remarkable therapeutic efficacy against blood cancers such as leukemia and lymphomas, but its effect is still limited due to the lack of well-defined antigens expressed by aberrant cells within tumors, the insufficient trafficking of administered T cells to the tumor sites, as well as immunosuppression induced by the tumor microenvironment (TME). In this study, we propose the adoptive transfer of photosensitizer (PS)-loaded cytotoxic T cells for a combinational photodynamic and cancer immunotherapy. Temoporfin (Foscan<sup>®</sup>), a clinically applicable porphyrin derivative, was loaded into OT-1 cells (PS-OT-1 cells). The PS-OT-1 cells efficiently produced a large amount of reactive oxygen species (ROS) under visible light irradiation in a culture; importantly, the combinational photodynamic therapy (PDT) and ACT with PS-OT-1 cells induced significant cytotoxicity compared to ACT alone with unloaded OT-1 cells. In murine lymphoma models, intravenously injected PS-OT-1 cells significantly inhibited tumor growth compared to unloaded OT-1 cells when the tumor tissues were locally irradiated with visible light. Collectively, this study suggests that combinational PDT and ACT mediated by PS-OT-1 cells provides a new approach for effective cancer immunotherapy.https://www.mdpi.com/1999-4923/15/4/1295cancer immunotherapyphotodynamic therapycombination therapyadoptive T cell therapycell-mediated drug delivery |
spellingShingle | André-René Blaudszun Woo Jun Kim Wooram Um Hong Yeol Yoon Man Kyu Shim Kwangmeyung Kim Adoptive Transfer of Photosensitizer-Loaded Cytotoxic T Cells for Combinational Photodynamic Therapy and Cancer Immuno-Therapy Pharmaceutics cancer immunotherapy photodynamic therapy combination therapy adoptive T cell therapy cell-mediated drug delivery |
title | Adoptive Transfer of Photosensitizer-Loaded Cytotoxic T Cells for Combinational Photodynamic Therapy and Cancer Immuno-Therapy |
title_full | Adoptive Transfer of Photosensitizer-Loaded Cytotoxic T Cells for Combinational Photodynamic Therapy and Cancer Immuno-Therapy |
title_fullStr | Adoptive Transfer of Photosensitizer-Loaded Cytotoxic T Cells for Combinational Photodynamic Therapy and Cancer Immuno-Therapy |
title_full_unstemmed | Adoptive Transfer of Photosensitizer-Loaded Cytotoxic T Cells for Combinational Photodynamic Therapy and Cancer Immuno-Therapy |
title_short | Adoptive Transfer of Photosensitizer-Loaded Cytotoxic T Cells for Combinational Photodynamic Therapy and Cancer Immuno-Therapy |
title_sort | adoptive transfer of photosensitizer loaded cytotoxic t cells for combinational photodynamic therapy and cancer immuno therapy |
topic | cancer immunotherapy photodynamic therapy combination therapy adoptive T cell therapy cell-mediated drug delivery |
url | https://www.mdpi.com/1999-4923/15/4/1295 |
work_keys_str_mv | AT andrereneblaudszun adoptivetransferofphotosensitizerloadedcytotoxictcellsforcombinationalphotodynamictherapyandcancerimmunotherapy AT woojunkim adoptivetransferofphotosensitizerloadedcytotoxictcellsforcombinationalphotodynamictherapyandcancerimmunotherapy AT wooramum adoptivetransferofphotosensitizerloadedcytotoxictcellsforcombinationalphotodynamictherapyandcancerimmunotherapy AT hongyeolyoon adoptivetransferofphotosensitizerloadedcytotoxictcellsforcombinationalphotodynamictherapyandcancerimmunotherapy AT mankyushim adoptivetransferofphotosensitizerloadedcytotoxictcellsforcombinationalphotodynamictherapyandcancerimmunotherapy AT kwangmeyungkim adoptivetransferofphotosensitizerloadedcytotoxictcellsforcombinationalphotodynamictherapyandcancerimmunotherapy |