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Title: Combined Treatment Effects of Radiation and Immunotherapy: Studies in an Autochthonous Prostate Cancer Model

Purpose: To optimize the combination of ionizing radiation and cellular immunotherapy using a preclinical autochthonous model of prostate cancer. Methods and Materials: Transgenic mice expressing a model antigen under a prostate-specific promoter were treated using a platform that integrates cone-beam CT imaging with 3-dimensional conformal therapy. Using this technology we investigated the immunologic and therapeutic effects of combining ionizing radiation with granulocyte/macrophage colony-stimulating factor-secreting cellular immunotherapy for prostate cancer in mice bearing autochthonous prostate tumors. Results: The combination of ionizing radiation and immunotherapy resulted in a significant decrease in pathologic tumor grade and gross tumor bulk that was not evident with either single-modality therapy. Furthermore, combinatorial therapy resulted in improved overall survival in a preventive metastasis model and in the setting of established micrometastases. Mechanistically, combined therapy resulted in an increase of the ratio of effector-to-regulatory T cells for both CD4 and CD8 tumor-infiltrating lymphocytes. Conclusions: Our preclinical model establishes a potential role for the use of combined radiation-immunotherapy in locally advanced prostate cancer, which warrants further exploration in a clinical setting.
Authors:
 [1] ; ;  [2] ;  [1] ;  [2] ; ; ; ;  [1] ;  [3] ;  [4] ;
  1. Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)
  2. Department of Radiation Oncology and Molecular Radiation Sciences, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)
  3. Department of Pathology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)
  4. (United States)
Publication Date:
OSTI Identifier:
22267948
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 87; Journal Issue: 4; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; COMBINED THERAPY; IMMUNOTHERAPY; IONIZING RADIATIONS; LYMPHOCYTES; METASTASES; NEOPLASMS; PROSTATE; TRANSGENIC MICE