Inhibition of glioma development by doxorubicin-photochemical internalization generated macrophage vaccine: A survival study in rats

Lina Nguyen; Catherine Christie; Steen J Madsen; Qian Peng; Kristian Berg; Henry Hirschberg

doi:10.1016/j.pdpdt.2022.102879

Inhibition of glioma development by doxorubicin-photochemical internalization generated macrophage vaccine: A survival study in rats

Photodiagnosis Photodyn Ther. 2022 Jun;38:102879. doi: 10.1016/j.pdpdt.2022.102879. Epub 2022 Apr 27.

Authors

Lina Nguyen¹, Catherine Christie², Steen J Madsen³, Qian Peng⁴, Kristian Berg⁵, Henry Hirschberg⁶

Affiliations

¹ Beckman Laser Institute and Medical Clinic, University of California, Irvine CA, 92612, USA. Electronic address: Linanguyen824@gmail.com.
² Beckman Laser Institute and Medical Clinic, University of California, Irvine CA, 92612, USA.
³ Department of Health Physics and Diagnostic Sciences, University of Nevada, Las Vegas, NV, 89154, USA.
⁴ Pathology Clinic, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310 Oslo, Norway.
⁵ Dept. of Radiation Biology, Rikshospitalet-Radiumhospitalet HF Medical Center, University of Oslo, Oslo, Norway.
⁶ Beckman Laser Institute and Medical Clinic, University of California, Irvine CA, 92612, USA; Department of Health Physics and Diagnostic Sciences, University of Nevada, Las Vegas, NV, 89154, USA.

PMID: 35489691
DOI: 10.1016/j.pdpdt.2022.102879

Abstract

Background: The process known as immunogenic cell death (ICD) is characterized by dead and dying cancer cells exposing and releasing so-called damage associated molecular patterns (DAMPs). ICD has been shown to enhance the efficacy of antigen presenting cell (APC) immunotherapy. Both anthracycline drugs such as doxorubicin (DOX), and photodynamic therapy (PDT) have been shown to be inducers of ICD. It was therefore hypothesized that combined PDT and DOX i.e. photochemical internalization of DOX (DOX-PCI) would increase ICD compared to DOX acting as a single agent.

Materials and methods: F98 glioma cells were treated with DOX-PCI in vitro and the ICD markers HMGB1, HSP70, and HSP90 were determined by ELISA assay. Peritoneal macrophages (Ma), obtained from Fisher rats acting as APCs, were co-incubated with dead F98 glioma cells killed via DOX or DOX-PCI treatment ex vivo. The pulsed Ma (Ma ^DOX or Ma ^DOX-PCI) were used to inoculate the animals either before (preventive) or after (curative) intra-cranially implantation of the glioma cells.

Results: F98 cells, treated with DOX-PCI in vitro, induced a significantly higher level of HGMB1, HSP70, and HSP90 than DOX acting alone. Ma ^DOX-PCI inoculated animals, in both preventive and curative protocols, had a pronounced survival benefit compared to either the non-treatment or Ma^DOX control groups. In the curative protocol, a second booster inoculation significantly improved survival, with 60% of the animals alive at day 60.

Conclusion: Macrophages primed with DOX-PCI treated glioma cells appeared to be highly effective as APCs and, when injected into host animals, could delay and, in some cases, prevent tumor development.

Keywords: Antigen presenting cell; Doxorubicin; Immunogenic cell death; Photochemical internalization; Photodynamic therapy.

MeSH terms

Animals
Cell Line, Tumor
Doxorubicin / pharmacology
Glioma* / drug therapy
Macrophages
Percutaneous Coronary Intervention*
Photochemotherapy* / methods
Rats
Vaccines* / metabolism
Vaccines* / therapeutic use

Substances

Vaccines
Doxorubicin