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Imaging Immune Response In vivo: Cytolytic Action of Genetically Altered T Cells Directed to Glioblastoma Multiforme

Lazovic, Jelena and Jensen, Michael C. and Ferkassian, Evette and Aguilar, Brenda and Raubitschek, Andrew and Jacobs, Russell E. (2008) Imaging Immune Response In vivo: Cytolytic Action of Genetically Altered T Cells Directed to Glioblastoma Multiforme. Clinical Cancer Research, 14 (12). pp. 3832-3839. ISSN 1078-0432. PMCID PMC2737486. https://resolver.caltech.edu/CaltechAUTHORS:20160201-103332308

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Abstract

Purpose: Clinical trials have commenced to evaluate the feasibility of targeting malignant gliomas with genetically engineered CTLs delivered directly to the tumor bed in the central nervous system. The objective of this study is to determine a suite of magnetic resonance imaging (MRI) measurements using an orthotopic xenograft murine model that can noninvasively monitor immunologically mediated tumor regression and reactive changes in the surrounding brain parenchyma. Experimental Design: Our preclinical therapeutic platform is based on CTL genetic modification to express a membrane tethered interleukin-13 (IL-13) cytokine chimeric T-cell antigen receptor. This enables selective binding and signal transduction on encountering the glioma-restricted IL-13 α2 receptor (IL-13Rα2). We used MRI to visualize immune responses following adoptive transfer of IL-13Rα2-specific CD8^+ CTL clones. Results: Based on MRI measurements, several phases following IL-13Rα2-specific T-cell adoptive transfer could be distinguished, all of which correlated well with glioblastoma regression confirmed on histology. The first detectable changes, 24 hours post-treatment, were significantly increased T_2 relaxation times and strongly enhanced signal on T_1-weighted postcontrast images. In the next phase, the apparent diffusion coefficient was significantly increased at 2 and 3 days post-treatment. In the last phase, at day 3 after IL-13Rα2-specific T-cell injection, the volume of hyperintense signal on T_1-weighted postcontrast image was significantly decreased, whereas apparent diffusion coefficient remained elevated. Conclusions: The present study indicates the feasibility of MRI to visualize different phases of immune response when IL-13Rα2-specific CTLs are administered directly to the glioma tumor bed. This will further the aim of better predicting clinical outcome following immunotherapy.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1158/1078-0432.CCR-07-5067 DOIArticle
http://clincancerres.aacrjournals.org/content/14/12/3832.abstractPublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737486/PubMed CentralArticle
ORCID:
AuthorORCID
Jacobs, Russell E.0000-0002-1382-8486
Additional Information:© 2008 American Association for Cancer Research. Received12/5/07; revised 3/12/08; accepted 3/21/08. Gordon and Betty Moore Foundation (Caltech Brain Imaging Center), NIH grants R01 EB000993 (R.E. Jacobs) and 1F32NS058164-01 (J. Lazovic), and National Center for Research Resources grant U24 RR021760 entitled Mouse BIRN (R.E. Jacobs).
Funders:
Funding AgencyGrant Number
Gordon and Betty Moore FoundationUNSPECIFIED
NIHR01 EB000993
NIH1F32NS058164-01
National Center for Research Resources (NCRR)U24 RR021760
Issue or Number:12
PubMed Central ID:PMC2737486
Record Number:CaltechAUTHORS:20160201-103332308
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160201-103332308
Official Citation:Imaging Immune Response In vivo: Cytolytic Action of Genetically Altered T Cells Directed to Glioblastoma Multiforme Jelena Lazovic, Michael C. Jensen, Evette Ferkassian, Brenda Aguilar, Andrew Raubitschek, and Russell E. Jacobs Clin Cancer Res June 15, 2008 14:3832-3839; doi:10.1158/1078-0432.CCR-07-5067
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64121
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:03 Feb 2016 20:38
Last Modified:03 Oct 2019 09:34

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