Antitumor Immunostimulatory Effect Via Cell-killing Action of a Novel Extracorporeal Blood Circulating Photodynamic Therapy System Using 5-aminolevulinic Acid

Overview

Journal Sci Rep

Specialty Science

Date 2025 Jan 8

PMID 39775122

Authors

Hidetaka Maegawa

Masayuki Kohashi

Yasuo Harada

Akira Tanaka

Shimpei Kajiwara

Takashi Fujimoto

Hidehiro Atagi

Kenta Kaneda

Affiliations

Soon will be listed here.

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.

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