Abstract

Simple SummaryRecent advances in treating cancer via stimulating an anti-tumor immune system response have resulted in extraordinary results for lymphomas and leukemias; however these therapies have not performed well in solid tumors. External beam therapies, such as radiotherapy, hyperthermia, and photodynamic therapy, that are clinically used for solid tumors are now being explored in combination with nanoparticle systems to stimulate a long-term anti-tumor immune system response. In this review, we detail the novel nanoparticle complexes that are being researched to activate an anti-tumor immune response in combination with external beam therapy in both the preclinical and clinical settings.Nanoparticles activated by external beams, such as ionizing radiation, laser light, or magnetic fields, have attracted significant research interest as a possible modality for treating solid tumors. From producing hyperthermic conditions to generating reactive oxygen species, a wide range of externally activated mechanisms have been explored for producing cytotoxicity within tumors with high spatiotemporal control. To further improve tumoricidal effects, recent trends in the literature have focused on stimulating the immune system through externally activated treatment strategies that result in immunogenic cell death. By releasing inflammatory compounds known to initiate an immune response, treatment methods can take advantage of immune system pathways for a durable and robust systemic anti-tumor response. In this review, we discuss recent advancements in radiosensitizing and hyperthermic nanoparticles that have been tuned for promoting immunogenic cell death. Our review covers both preclinical and clinical results, as well as an overview of possible future work.

Highlights

  • In recent years, immunotherapies utilizing chimeric antigen receptor (CAR) T cells and immune checkpoint blockades have shown remarkable success in treating cancer

  • We explore examples of nanotechnology being used in external beam therapies to stimulate damage-associated molecular patterns (DAMPs), pro-inflammatory cytokines, and tumor-related antigens

  • An additional clinical study was performed by Maier-Hauff et al [32], where 59 recurrent glioblastoma patients were treated with hyperthermia mediated via iron oxide nanoparticles in combination with a reduced dose of radiotherapy, which resulted in an increased overall survival following first tumor recurrence

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Summary

Introduction

Immunotherapies utilizing chimeric antigen receptor (CAR) T cells and immune checkpoint blockades have shown remarkable success in treating cancer. To overcome the current limitations in treating solid tumors via immunotherapies, methods that stimulate an antitumor immune response via immunogenic cell death (ICD) have garnered significant research attention. External beam therapies, such as radiotherapy, photodynamic therapy, and hyperthermia, have been shown to cause ICD, Cancers 2020, 12, 3559; doi:10.3390/cancers12123559 www.mdpi.com/journal/cancers. Cancers 2020, 12, 3559 which can stimulate antitumor immune system effects that inhibit both primary tumor growth and secondary metastases and confer long-term immunity against re-challenge [2] These externally activated systems are often mediated via nanoparticle materials that can both enhance immunogenic effects by increasing the efficacy of these therapies as well as act as drug-delivery vehicles for the local release of immunotherapeutics. We reviewed trends in the current literature analyzing the immunogenicity of these externally activated cancer treatments

Hyperthermia
Photothermal Therapy
Magnetic Field
Photodynamic Therapy
Radiosensitizers
Potential Limitations
Findings
Conclusions
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