Antitumor immunostimulatory effect via cell-killing action of a novel extracorporeal blood circulating photodynamic therapy system using 5-aminolevulinic acid
Abstract This study investigated whether intravenous administration of tumor cells killed by photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) had antitumor effects on distal tumors. Furthermore, a novel extracorporeal blood circulating 5-ALA/PDT system was developed. 5-ALA/PDT- (low or...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-84861-8 |
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| author | Hidetaka Maegawa Masayuki Kohashi Yasuo Harada Akira Tanaka Shimpei Kajiwara Takashi Fujimoto Hidehiro Atagi Kenta Kaneda |
| author_facet | Hidetaka Maegawa Masayuki Kohashi Yasuo Harada Akira Tanaka Shimpei Kajiwara Takashi Fujimoto Hidehiro Atagi Kenta Kaneda |
| author_sort | Hidetaka Maegawa |
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| description | Abstract This study investigated whether intravenous administration of tumor cells killed by photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) had antitumor effects on distal tumors. Furthermore, a novel extracorporeal blood circulating 5-ALA/PDT system was developed. 5-ALA/PDT- (low or high irradiation) or anticancer drug–treated cells were intravenously administered to rats in a glioma cancer model. CD8+ T cell infiltration into the tumor and expression of calreticulin were examined. The cell-killing effect in the circulating PDT system and protoporphyrin IX (PpIX) accumulation were evaluated. An antitumor effect was observed only with preadministration of low-irradiated 5-ALA/PDT-treated cells and was characterized by the infiltration of CD8+ T cells into the tumor. In low-irradiated cells, several types of cell death were observed, and cell surface calreticulin expression increased over time. A method for the intravenous administration of 5-ALA/PDT-treated cells along with extracorporeal blood circulation was then developed to target hematologic malignancies. Gradually cell death in the circulating PDT system and tumor-specific PpIX accumulation was confirmed using hematopoietic tumor cells. Thus, the extracorporeal blood circulating 5-ALA/PDT system has a direct cell-killing effect and an antitumor effect via induced immune activity and illustrates a new therapeutic strategy for hematologic malignancies. |
| format | Article |
| id | doaj-art-086807937a0048c4860e13924ccb5912 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-086807937a0048c4860e13924ccb59122025-01-12T12:22:11ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-024-84861-8Antitumor immunostimulatory effect via cell-killing action of a novel extracorporeal blood circulating photodynamic therapy system using 5-aminolevulinic acidHidetaka Maegawa0Masayuki Kohashi1Yasuo Harada2Akira Tanaka3Shimpei Kajiwara4Takashi Fujimoto5Hidehiro Atagi6Kenta Kaneda7Research Division, JIMRO Co., Ltd.Medical Equipment Development Department, Development Division, Otsuka Electronics Co., Ltd.Department of Drug Modality Development, Osaka Research Center for Drug Discovery, New Drug Research Division, Otsuka Pharmaceutical Co., Ltd.Medical Equipment Development Department, Development Division, Otsuka Electronics Co., Ltd.Medical Equipment Development Department, Development Division, Otsuka Electronics Co., Ltd.Medical Equipment Development Department, Development Division, Otsuka Electronics Co., Ltd.Medical Equipment Development Department, Development Division, Otsuka Electronics Co., Ltd.Research Division, JIMRO Co., Ltd.Abstract This study investigated whether intravenous administration of tumor cells killed by photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) had antitumor effects on distal tumors. Furthermore, a novel extracorporeal blood circulating 5-ALA/PDT system was developed. 5-ALA/PDT- (low or high irradiation) or anticancer drug–treated cells were intravenously administered to rats in a glioma cancer model. CD8+ T cell infiltration into the tumor and expression of calreticulin were examined. The cell-killing effect in the circulating PDT system and protoporphyrin IX (PpIX) accumulation were evaluated. An antitumor effect was observed only with preadministration of low-irradiated 5-ALA/PDT-treated cells and was characterized by the infiltration of CD8+ T cells into the tumor. In low-irradiated cells, several types of cell death were observed, and cell surface calreticulin expression increased over time. A method for the intravenous administration of 5-ALA/PDT-treated cells along with extracorporeal blood circulation was then developed to target hematologic malignancies. Gradually cell death in the circulating PDT system and tumor-specific PpIX accumulation was confirmed using hematopoietic tumor cells. Thus, the extracorporeal blood circulating 5-ALA/PDT system has a direct cell-killing effect and an antitumor effect via induced immune activity and illustrates a new therapeutic strategy for hematologic malignancies.https://doi.org/10.1038/s41598-024-84861-8Aminolevulinic acidPhotodynamic therapyExtracorporeal blood circulationAntitumor effectHematological malignancies |
| spellingShingle | Hidetaka Maegawa Masayuki Kohashi Yasuo Harada Akira Tanaka Shimpei Kajiwara Takashi Fujimoto Hidehiro Atagi Kenta Kaneda Antitumor immunostimulatory effect via cell-killing action of a novel extracorporeal blood circulating photodynamic therapy system using 5-aminolevulinic acid Scientific Reports Aminolevulinic acid Photodynamic therapy Extracorporeal blood circulation Antitumor effect Hematological malignancies |
| title | Antitumor immunostimulatory effect via cell-killing action of a novel extracorporeal blood circulating photodynamic therapy system using 5-aminolevulinic acid |
| title_full | Antitumor immunostimulatory effect via cell-killing action of a novel extracorporeal blood circulating photodynamic therapy system using 5-aminolevulinic acid |
| title_fullStr | Antitumor immunostimulatory effect via cell-killing action of a novel extracorporeal blood circulating photodynamic therapy system using 5-aminolevulinic acid |
| title_full_unstemmed | Antitumor immunostimulatory effect via cell-killing action of a novel extracorporeal blood circulating photodynamic therapy system using 5-aminolevulinic acid |
| title_short | Antitumor immunostimulatory effect via cell-killing action of a novel extracorporeal blood circulating photodynamic therapy system using 5-aminolevulinic acid |
| title_sort | antitumor immunostimulatory effect via cell killing action of a novel extracorporeal blood circulating photodynamic therapy system using 5 aminolevulinic acid |
| topic | Aminolevulinic acid Photodynamic therapy Extracorporeal blood circulation Antitumor effect Hematological malignancies |
| url | https://doi.org/10.1038/s41598-024-84861-8 |
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