Combined immunotherapy with Listeria monocytogenes-based PSA vaccine and radiation therapy leads to a therapeutic response in a murine model of prostate cancer.
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.
Department of Radiation Oncology, UT Southwestern Medical Center, 5801 Forest Park Rd., Dallas, TX, 75390-9183, USA. Raquibul.Hannan@UTSW.edu
Raquibul
R
Hannan
Huagang
H
Zhang
Anu
A
Wallecha
Reshma
R
Singh
Laibin
L
Liu
Patrice
P
Cohen
Alan
A
Alfieri
John
J
Rothman
Chandan
C
Guha
D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology / Q000494:pharmacology; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017430:Prostate-Specific Antigen / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000532:radiotherapy / Q000628:therapy*; D011897:Random Allocation; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D001428:Bacterial Vaccines; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma; D017430:Prostate-Specific Antigen