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

Authors

  • Raquibul Hannan
    • Department of Radiation OncologyUT Southwestern Medical Center
  • Huagang Zhang
    • Department of Radiation Oncology, Albert Einstein College of MedicineMontefiore Medical Centre
  • Anu Wallecha
    • Advaxis Inc.
  • Reshma Singh
    • Advaxis Inc.
  • Laibin Liu
    • Department of Radiation Oncology, Albert Einstein College of MedicineMontefiore Medical Centre
  • Patrice Cohen
    • Department of Radiation Oncology, Albert Einstein College of MedicineMontefiore Medical Centre
  • Alan Alfieri
    • Department of Radiation Oncology, Albert Einstein College of MedicineMontefiore Medical Centre
  • John Rothman
    • Advaxis Inc.
    • Department of Radiation Oncology, Albert Einstein College of MedicineMontefiore Medical Centre
    • Department of Pathology, Albert Einstein College of MedicineMontefiore Medical Center
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