Combined immunotherapy with Listeria monocytogenes-based PSA vaccine and radiation therapy leads to a therapeutic response in a murine model of prostate cancer

Cancer Immunol Immunother. 2012 Dec;61(12):2227-38. doi: 10.1007/s00262-012-1257-x. Epub 2012 May 27.


Radiation therapy (RT) is an integral part of prostate cancer treatment across all stages and risk groups. Immunotherapy using a live, attenuated, Listeria monocytogenes-based vaccines have been shown previously to be highly efficient in stimulating anti-tumor responses to impact on the growth of established tumors in different tumor models. Here, we evaluated the combination of RT and immunotherapy using Listeria monocytogenes-based vaccine (ADXS31-142) in a mouse model of prostate cancer. Mice bearing PSA-expressing TPSA23 tumor were divided to 5 groups receiving no treatment, ADXS31-142, RT (10 Gy), control Listeria vector and combination of ADXS31-142 and RT. Tumor growth curve was generated by measuring the tumor volume biweekly. Tumor tissue, spleen, and sera were harvested from each group for IFN-γ ELISpot, intracellular cytokine assay, tetramer analysis, and immunofluorescence staining. There was a significant tumor growth delay in mice that received combined ADXS31-142 and RT treatment as compared with mice of other cohorts and this combined treatment causes complete regression of their established tumors in 60 % of the mice. ELISpot and immunohistochemistry of CD8+ cytotoxic T Lymphocytes (CTL) showed a significant increase in IFN-γ production in mice with combined treatment. Tetramer analysis showed a fourfold and a greater than 16-fold increase in PSA-specific CTLs in animals receiving ADXS31-142 alone and combination treatment, respectively. A similar increase in infiltration of CTLs was observed in the tumor tissues. Combination therapy with RT and Listeria PSA vaccine causes significant tumor regression by augmenting PSA-specific immune response and it could serve as a potential treatment regimen for prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacterial Vaccines / immunology
  • Bacterial Vaccines / pharmacology
  • Cancer Vaccines / immunology
  • Cancer Vaccines / pharmacology*
  • Cell Line, Tumor
  • Combined Modality Therapy / methods
  • Epitopes, T-Lymphocyte / immunology
  • Immunotherapy / methods
  • Interferon-gamma / immunology
  • Listeria monocytogenes / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Prostate-Specific Antigen / immunology*
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / radiotherapy
  • Prostatic Neoplasms / therapy*
  • Random Allocation
  • Spleen / immunology
  • T-Lymphocytes, Cytotoxic / immunology


  • Bacterial Vaccines
  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • Interferon-gamma
  • Prostate-Specific Antigen