Antitumor immunostimulatory effect via cell-killing action of a novel extracorporeal blood circulating photodynamic therapy system using 5-aminolevulinic acid.

in Scientific reports by Hidetaka Maegawa, Masayuki Kohashi, Yasuo Harada, Akira Tanaka, Shimpei Kajiwara, Takashi Fujimoto, Hidehiro Atagi, Kenta Kaneda

TLDR

  • The study found that low-irradiated 5-ALA/PDT-treated cells have an antitumor effect by inducing CD8T cell infiltration into the tumor and increasing calreticulin expression.

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. CD8T 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 CD8T 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.

Overview

  • The study investigated the antitumor effects of intravenously administered tumor cells killed by photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) on distal tumors.
  • A novel extracorporeal blood circulating 5-ALA/PDT system was developed for the treatment of hematologic malignancies.
  • The study aimed to test the hypothesis that preadministration of low-irradiated 5-ALA/PDT-treated cells would have an antitumor effect in a glioma cancer model.

Comparative Analysis & Findings

  • An antitumor effect was observed only with preadministration of low-irradiated 5-ALA/PDT-treated cells, which was characterized by infiltration of CD8T cells into the tumor.
  • Low-irradiated cells showed several types of cell death and increased cell surface calreticulin expression over time.
  • The extracorporeal blood circulating 5-ALA/PDT system had a direct cell-killing effect and an antitumor effect via induced immune activity in a hematopoietic tumor cell model

Implications and Future Directions

  • The study provides a new therapeutic strategy for hematologic malignancies by developing an extracorporeal blood circulating 5-ALA/PDT system.
  • Future studies should focus on optimizing the dosage and timing of the low-irradiated 5-ALA/PDT-treated cells to enhance the antitumor effect.
  • The system could be further developed for the treatment of other types of cancer and diseases
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