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Radiotherapy-Activated Hafnium Oxide Nanoparticles Produce Abscopal Effect in a Mouse Colorectal Cancer Model
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Radiotherapy-Activated Hafnium Oxide Nanoparticles Produce Abscopal Effect in a Mouse Colorectal Cancer Model
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Journal Article
Radiotherapy-Activated Hafnium Oxide Nanoparticles Produce Abscopal Effect in a Mouse Colorectal Cancer Model
2020
Overview
Despite tremendous results achieved by immune checkpoint inhibitors, most patients are not responders, mainly because of the lack of a pre-existing anti-tumor immune response. Thus, solutions to efficiently prime this immune response are currently under intensive investigations. Radiotherapy elicits cancer cell death, generating an antitumor-specific T cell response, turning tumors in personalized in situ vaccines, with potentially systemic effects (abscopal effect). Nonetheless, clinical evidence of sustained anti-tumor immunity as abscopal effect are rare.
Hafnium oxide nanoparticles (NBTXR3) have been designed to increase energy dose deposit within cancer cells. We examined the effect of radiotherapy-activated NBTXR3 on anti-tumor immune response activation and abscopal effect production using a mouse colorectal cancer model.
We demonstrate that radiotherapy-activated NBTXR3 kill more cancer cells than radiotherapy alone, significantly increase immune cell infiltrates both in treated and in untreated distant tumors, generating an abscopal effect dependent on CD8+ lymphocyte T cells.
These data show that radiotherapy-activated NBTXR3 could increase local and distant tumor control through immune system priming. Our results may have important implications for immunotherapeutic agent combination with radiotherapy.
Publisher
Dove Medical Press Limited,Taylor & Francis Ltd,Dove,Dove Medical Press
Subject
/ Animals
/ Antineoplastic Agents, Immunological - chemistry
/ Antineoplastic Agents, Immunological - pharmacokinetics
/ Antineoplastic Agents, Immunological - pharmacology
/ CD8-Positive T-Lymphocytes - immunology
/ Colorectal Neoplasms - drug therapy
/ Colorectal Neoplasms - immunology
/ Colorectal Neoplasms - radiotherapy
/ Female
/ Hafnium
/ Metal Nanoparticles - administration & dosage
/ Metal Nanoparticles - chemistry
/ nbtxr3
/ Neoplasms, Experimental - drug therapy
/ Neoplasms, Experimental - immunology
/ Neoplasms, Experimental - radiotherapy
/ T cells
/ tils
/ Tumors
/ Vaccines
