Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy.
The anecdotal reports of promising results seen with immunotherapy and radiation in advanced malignancies have prompted several trials combining immunotherapy and radiation. However, the ideal timing of immunotherapy with radiation has not been clarified. Tumor bearing mice were treated with 20Gy ra...
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2016-01-01
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doaj-2781218293ae4eadb113a4a1d59defb72020-11-24T22:21:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01116e015716410.1371/journal.pone.0157164Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy.Kristina H YoungJason R BairdTalicia SavageBenjamin CottamDavid FriedmanShelly BambinaDavid J MessenheimerBernard FoxPippa NewellKeith S BahjatMichael J GoughMarka R CrittendenThe anecdotal reports of promising results seen with immunotherapy and radiation in advanced malignancies have prompted several trials combining immunotherapy and radiation. However, the ideal timing of immunotherapy with radiation has not been clarified. Tumor bearing mice were treated with 20Gy radiation delivered only to the tumor combined with either anti-CTLA4 antibody or anti-OX40 agonist antibody. Immunotherapy was delivered at a single timepoint around radiation. Surprisingly, the optimal timing of these therapies varied. Anti-CTLA4 was most effective when given prior to radiation therapy, in part due to regulatory T cell depletion. Administration of anti-OX40 agonist antibody was optimal when delivered one day following radiation during the post-radiation window of increased antigen presentation. Combination treatment of anti-CTLA4, radiation, and anti-OX40 using the ideal timing in a transplanted spontaneous mammary tumor model demonstrated tumor cures. These data demonstrate that the combination of immunotherapy and radiation results in improved therapeutic efficacy, and that the ideal timing of administration with radiation is dependent on the mechanism of action of the immunotherapy utilized.http://europepmc.org/articles/PMC4900555?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kristina H Young Jason R Baird Talicia Savage Benjamin Cottam David Friedman Shelly Bambina David J Messenheimer Bernard Fox Pippa Newell Keith S Bahjat Michael J Gough Marka R Crittenden |
spellingShingle |
Kristina H Young Jason R Baird Talicia Savage Benjamin Cottam David Friedman Shelly Bambina David J Messenheimer Bernard Fox Pippa Newell Keith S Bahjat Michael J Gough Marka R Crittenden Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy. PLoS ONE |
author_facet |
Kristina H Young Jason R Baird Talicia Savage Benjamin Cottam David Friedman Shelly Bambina David J Messenheimer Bernard Fox Pippa Newell Keith S Bahjat Michael J Gough Marka R Crittenden |
author_sort |
Kristina H Young |
title |
Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy. |
title_short |
Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy. |
title_full |
Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy. |
title_fullStr |
Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy. |
title_full_unstemmed |
Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy. |
title_sort |
optimizing timing of immunotherapy improves control of tumors by hypofractionated radiation therapy. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
The anecdotal reports of promising results seen with immunotherapy and radiation in advanced malignancies have prompted several trials combining immunotherapy and radiation. However, the ideal timing of immunotherapy with radiation has not been clarified. Tumor bearing mice were treated with 20Gy radiation delivered only to the tumor combined with either anti-CTLA4 antibody or anti-OX40 agonist antibody. Immunotherapy was delivered at a single timepoint around radiation. Surprisingly, the optimal timing of these therapies varied. Anti-CTLA4 was most effective when given prior to radiation therapy, in part due to regulatory T cell depletion. Administration of anti-OX40 agonist antibody was optimal when delivered one day following radiation during the post-radiation window of increased antigen presentation. Combination treatment of anti-CTLA4, radiation, and anti-OX40 using the ideal timing in a transplanted spontaneous mammary tumor model demonstrated tumor cures. These data demonstrate that the combination of immunotherapy and radiation results in improved therapeutic efficacy, and that the ideal timing of administration with radiation is dependent on the mechanism of action of the immunotherapy utilized. |
url |
http://europepmc.org/articles/PMC4900555?pdf=render |
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