Positron emission tomography imaging with 89Zr-labeled anti-CD8 cys-diabody reveals CD8+ cell infiltration during oncolytic virus therapy in a glioma murine model

Abstract Determination of treatment response to immunotherapy in glioblastoma multiforme (GBM) is a process which can take months. Detection of CD8+ T cell recruitment to the tumor with a noninvasive imaging modality such as positron emission tomography (PET) may allow for tumor characterization and...

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Autores principales:	Benjamin B. Kasten, Hailey A. Houson, Jennifer M. Coleman, Jianmei W. Leavenworth, James M. Markert, Anna M. Wu, Felix Salazar, Richard Tavaré, Adriana V. F. Massicano, G. Yancey Gillespie, Suzanne E. Lapi, Jason M. Warram, Anna G. Sorace
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5121b4300f984e959794f9b641be16e2
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spelling	oai:doaj.org-article:5121b4300f984e959794f9b641be16e22021-12-02T18:47:07ZPositron emission tomography imaging with 89Zr-labeled anti-CD8 cys-diabody reveals CD8+ cell infiltration during oncolytic virus therapy in a glioma murine model10.1038/s41598-021-94887-x2045-2322https://doaj.org/article/5121b4300f984e959794f9b641be16e22021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94887-xhttps://doaj.org/toc/2045-2322Abstract Determination of treatment response to immunotherapy in glioblastoma multiforme (GBM) is a process which can take months. Detection of CD8+ T cell recruitment to the tumor with a noninvasive imaging modality such as positron emission tomography (PET) may allow for tumor characterization and early evaluation of therapeutic response to immunotherapy. In this study, we utilized 89Zr-labeled anti-CD8 cys-diabody-PET to provide proof-of-concept to detect CD8+ T cell immune response to oncolytic herpes simplex virus (oHSV) M002 immunotherapy in a syngeneic GBM model. Immunocompetent mice (n = 16) were implanted intracranially with GSC005 GBM tumors, and treated with intratumoral injection of oHSV M002 or saline control. An additional non-tumor bearing cohort (n = 4) receiving oHSV M002 treatment was also evaluated. Mice were injected with 89Zr-labeled anti-CD8 cys-diabody seven days post oHSV administration and imaged with a preclinical PET scanner. Standardized uptake value (SUV) was quantified. Ex vivo tissue analyses included autoradiography and immunohistochemistry. PET imaging showed significantly higher SUV in tumors which had been treated with M002 compared to those without M002 treatment (p = 0.0207) and the non-tumor bearing M002 treated group (p = 0.0021). Accumulation in target areas, especially the spleen, was significantly reduced by blocking with the non-labeled diabody (p < 0.001). Radioactive probe accumulation in brains was consistent with CD8+ cell trafficking patterns after oHSV treatment. This PET imaging strategy could aid in distinguishing responders from non-responders during immunotherapy of GBM.Benjamin B. KastenHailey A. HousonJennifer M. ColemanJianmei W. LeavenworthJames M. MarkertAnna M. WuFelix SalazarRichard TavaréAdriana V. F. MassicanoG. Yancey GillespieSuzanne E. LapiJason M. WarramAnna G. SoraceNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Benjamin B. Kasten Hailey A. Houson Jennifer M. Coleman Jianmei W. Leavenworth James M. Markert Anna M. Wu Felix Salazar Richard Tavaré Adriana V. F. Massicano G. Yancey Gillespie Suzanne E. Lapi Jason M. Warram Anna G. Sorace Positron emission tomography imaging with 89Zr-labeled anti-CD8 cys-diabody reveals CD8+ cell infiltration during oncolytic virus therapy in a glioma murine model
description	Abstract Determination of treatment response to immunotherapy in glioblastoma multiforme (GBM) is a process which can take months. Detection of CD8+ T cell recruitment to the tumor with a noninvasive imaging modality such as positron emission tomography (PET) may allow for tumor characterization and early evaluation of therapeutic response to immunotherapy. In this study, we utilized 89Zr-labeled anti-CD8 cys-diabody-PET to provide proof-of-concept to detect CD8+ T cell immune response to oncolytic herpes simplex virus (oHSV) M002 immunotherapy in a syngeneic GBM model. Immunocompetent mice (n = 16) were implanted intracranially with GSC005 GBM tumors, and treated with intratumoral injection of oHSV M002 or saline control. An additional non-tumor bearing cohort (n = 4) receiving oHSV M002 treatment was also evaluated. Mice were injected with 89Zr-labeled anti-CD8 cys-diabody seven days post oHSV administration and imaged with a preclinical PET scanner. Standardized uptake value (SUV) was quantified. Ex vivo tissue analyses included autoradiography and immunohistochemistry. PET imaging showed significantly higher SUV in tumors which had been treated with M002 compared to those without M002 treatment (p = 0.0207) and the non-tumor bearing M002 treated group (p = 0.0021). Accumulation in target areas, especially the spleen, was significantly reduced by blocking with the non-labeled diabody (p < 0.001). Radioactive probe accumulation in brains was consistent with CD8+ cell trafficking patterns after oHSV treatment. This PET imaging strategy could aid in distinguishing responders from non-responders during immunotherapy of GBM.
format	article
author	Benjamin B. Kasten Hailey A. Houson Jennifer M. Coleman Jianmei W. Leavenworth James M. Markert Anna M. Wu Felix Salazar Richard Tavaré Adriana V. F. Massicano G. Yancey Gillespie Suzanne E. Lapi Jason M. Warram Anna G. Sorace
author_facet	Benjamin B. Kasten Hailey A. Houson Jennifer M. Coleman Jianmei W. Leavenworth James M. Markert Anna M. Wu Felix Salazar Richard Tavaré Adriana V. F. Massicano G. Yancey Gillespie Suzanne E. Lapi Jason M. Warram Anna G. Sorace
author_sort	Benjamin B. Kasten
title	Positron emission tomography imaging with 89Zr-labeled anti-CD8 cys-diabody reveals CD8+ cell infiltration during oncolytic virus therapy in a glioma murine model
title_short	Positron emission tomography imaging with 89Zr-labeled anti-CD8 cys-diabody reveals CD8+ cell infiltration during oncolytic virus therapy in a glioma murine model
title_full	Positron emission tomography imaging with 89Zr-labeled anti-CD8 cys-diabody reveals CD8+ cell infiltration during oncolytic virus therapy in a glioma murine model
title_fullStr	Positron emission tomography imaging with 89Zr-labeled anti-CD8 cys-diabody reveals CD8+ cell infiltration during oncolytic virus therapy in a glioma murine model
title_full_unstemmed	Positron emission tomography imaging with 89Zr-labeled anti-CD8 cys-diabody reveals CD8+ cell infiltration during oncolytic virus therapy in a glioma murine model
title_sort	positron emission tomography imaging with 89zr-labeled anti-cd8 cys-diabody reveals cd8+ cell infiltration during oncolytic virus therapy in a glioma murine model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5121b4300f984e959794f9b641be16e2
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Positron emission tomography imaging with 89Zr-labeled anti-CD8 cys-diabody reveals CD8+ cell infiltration during oncolytic virus therapy in a glioma murine model

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