Cancer Immunology, Immunotherapy

, Volume 61, Issue 12, pp 2227–2238

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

  • Raquibul Hannan
  • Huagang Zhang
  • Anu Wallecha
  • Reshma Singh
  • Laibin Liu
  • Patrice Cohen
  • Alan Alfieri
  • John Rothman
  • Chandan Guha
Original article

DOI: 10.1007/s00262-012-1257-x

Cite this article as:
Hannan, R., Zhang, H., Wallecha, A. et al. Cancer Immunol Immunother (2012) 61: 2227. doi:10.1007/s00262-012-1257-x

Abstract

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.

Keywords

Radiation therapyListeria PSA vaccineImmunotherapyProstate cancer

Supplementary material

262_2012_1257_MOESM1_ESM.tif (3.6 mb)
Supplemental Figure 1: Tumor response in representative mice on d34 from each of the cohorts: A) PSA Vaccine, B), PSA Vaccine +RT, C)RT Alone, D) No Treatment and E) Control Vaccine. (TIFF 3668 kb)
262_2012_1257_MOESM2_ESM.tif (277 kb)
Supplemental Figure 2: Representative wells after subjecting the splenocytes from each cohort to ELISpot analysis. A) Non-specific stimulation with PMA, B) Negative control stimulation with BSA, and C-G stimulation with PSA, C) PSA Vaccine, D), PSA Vaccine +RT, E)RT Alone, F) No Treatment and G) Control Vaccine. (TIFF 276 kb)
262_2012_1257_MOESM3_ESM.tif (3.4 mb)
Supplemental Figure 3: FACS analysis for IFN-γ in CD8+CD3+ cells.  A) PSA Vaccine, B), PSA Vaccine +RT, C)RT Alone, D) No Treatment and E) Control Vaccine. (TIFF 3480 kb)

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Raquibul Hannan
    • 1
  • Huagang Zhang
    • 2
  • Anu Wallecha
    • 4
  • Reshma Singh
    • 4
  • Laibin Liu
    • 2
  • Patrice Cohen
    • 2
  • Alan Alfieri
    • 2
  • John Rothman
    • 4
  • Chandan Guha
    • 2
    • 3
  1. 1.Department of Radiation OncologyUT Southwestern Medical CenterDallasUSA
  2. 2.Department of Radiation Oncology, Albert Einstein College of MedicineMontefiore Medical CentreBronxUSA
  3. 3.Department of Pathology, Albert Einstein College of MedicineMontefiore Medical CenterBronxUSA
  4. 4.Advaxis Inc.PrincetonUSA