Imaging Immune Response In vivo: Cytolytic Action of Genetically Altered T Cells Directed to Glioblastoma Multiforme
Open Access
- 15 June 2008
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 14 (12), 3832-3839
- https://doi.org/10.1158/1078-0432.ccr-07-5067
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 T2 relaxation times and strongly enhanced signal on T1-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 T1-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.Keywords
This publication has 32 references indexed in Scilit:
- Therapeutic Vaccination against Murine Lymphoma by Intratumoral Injection of Recombinant Fowlpox Virus Encoding CD40 LigandCancer Research, 2007
- Survival analysis in patients with glioblastoma multiforme: Predictive value of choline‐to‐n‐acetylaspartate index, apparent diffusion coefficient, and relative cerebral blood volumeJournal of Magnetic Resonance Imaging, 2004
- Water diffusion in a rat glioma during ganciclovir‐thymidine kinase gene therapy‐induced programmed cell death in vivo: Correlation with cell densityJournal of Magnetic Resonance Imaging, 2004
- Pretreatment Prediction of Brain Tumors Response to Radiation Therapy Using High b-Value Diffusion-Weighted MRINeoplasia, 2004
- T Cell AnergyAnnual Review of Immunology, 2003
- Interleukin-13 Receptor-Directed Cytotoxin for Malignant Glioma Therapy: From Bench to BedsideJournal of Neuro-Oncology, 2003
- Monitoring response to convection-enhanced taxol delivery in brain tumor patients using diffusion-weighted magnetic resonance imaging.2001
- Simultaneous correction of ghost and geometric distortion artifacts in EPI using a multiecho reference scanIEEE Transactions on Medical Imaging, 2001
- Diffusion Magnetic Resonance Imaging: an Early Surrogate Marker of Therapeutic Efficacy in Brain TumorsJNCI Journal of the National Cancer Institute, 2000
- Early Increases in Breast Tumor Xenograft Water Mobility in Response to Paclitaxel Therapy Detected by Non-Invasive Diffusion Magnetic Resonance ImagingNeoplasia, 1999