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.
Written by:
Wada S, Harris TJ, Tryggestad E, Yoshimura K, Zeng J, Yen HR, Getnet D, Grosso JF, Bruno TC, De Marzo AM, Netto GJ, Pardoll DM, Deweese TL, Wong J, Drake CG. Are you the author?
Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Reference: Int J Radiat Oncol Biol Phys. 2013 Sep 21. pii: S0360-3016(13)02853-8.
doi: 10.1016/j.ijrobp.2013.07.015
PubMed Abstract
PMID: 24064321
UroToday.com Prostate Cancer Immunotherapy Section
