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Title:
Combined immunotherapy with Listeria monocytogenes-based PSA vaccine and radiation therapy leads to a therapeutic response in a murine model of prostate cancer | Cancer Immunology, Immunotherapy
Description:
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.
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Keywords {🔍}
article, google, scholar, pubmed, cancer, cas, prostate, vaccine, tumor, immunotherapy, listeria, psa, radiation, cells, therapy, immunol, oncol, treatment, radiotherapy, clin, antigen, paterson, int, combined, response, tumors, med, schlom, res, monocytogenes, combination, mice, cell, patients, phase, hodge, immunother, analysis, wallecha, guha, vaccines, antitumor, growth, ctl, access, biol, study, human, prostatespecific, chen,
Topics {✒️}
hla-a2-restricted ny-eso-1b peptide poxviral-based psa-targeted immunotherapy spontaneous cd8+ t-cell response vaccine-mediated t-cell killing listeria monocytogenes-based vaccines psa-specific cd8+ ctl responses month download article/chapter stimulating anti-tumor responses long-term prognostic significance radiation-induced ifn-gamma production castration-resistant prostate cancer related subjects listeria monocytogenes-based vaccine total prostate-specific antigen therapeutic cancer vaccines reshma singh & john rothman article cancer immunology uvc light-induced apoptosis intermediate-risk prostate cancer listeria monocytogenes enhances dose-escalation study localized prostate cancer full article pdf long-term results e7 induce qualitatively lm-llo-e7 recombinant canarypox virus immune response targeting restricted ctl epitope randomized controlled trial prostate specific antigen prostate-specific antigen human papilloma virus-16 privacy choices/manage cookies recombinant cancer vaccine listeria psa vaccine broad antitumor response cell activating therapy tumor-bearing hosts radiation therapy leads synergizing radiation therapy local radiation therapy external beam radiation metastatic lung cancer metastatic prostate tumors listeria-induced macrophages current vaccination strategies advanced prostate cancer prostate cancer recurrence tumors alters phenotype
Questions {❓}
- Dasu A (2007) Is the alpha/beta value for prostate tumours low enough to be safely used in clinical trials?
- Fowler J, Chappell R, Ritter M (2001) Is alpha/beta for prostate tumors really low?
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headline:Combined immunotherapy with Listeria monocytogenes-based PSA vaccine and radiation therapy leads to a therapeutic response in a murine model of prostate cancer
description: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.
datePublished:2012-05-27T00:00:00Z
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Radiation therapy
Listeria PSA vaccine
Immunotherapy
Prostate cancer
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Cancer Research
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headline:Combined immunotherapy with Listeria monocytogenes-based PSA vaccine and radiation therapy leads to a therapeutic response in a murine model of prostate cancer
description: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.
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