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Int J Radiat Oncol Biol Phys. 2013 Nov 15;87(4):769-76. doi: 10.1016/j.ijrobp.2013.07.015. Epub 2013 Sep 21.

Combined treatment effects of radiation and immunotherapy: studies in an autochthonous prostate cancer model.

Author information

1
Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Abstract

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.

PMID:
24064321
PMCID:
PMC4417352
DOI:
10.1016/j.ijrobp.2013.07.015
[Indexed for MEDLINE]
Free PMC Article

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