Low‐dose total body irradiation augments the therapeutic effect of interleukin‐2 in a mouse model for metastatic malignant melanoma

Safwat, Akmal; Aggerholm, Ninna; Roitt, Ivan M.; Overgaard, Jens; Hokland, Marianne

doi:10.1046/j.1359-4117.2003.01093.x

Cited by 18 publications

(9 citation statements)

References 17 publications

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“…These data extend our studies using IL-3 retrovirus-transfected fibrosarcoma tumors 11 and Adv-IL3 with a constitutive promoter, 16 as well as being consistent with results of others in other tumor models. 1,20,21 The increased response to RT in this system was not due to IL-3-induced alteration in the intrinsic cellular radiosensitivity of the tumor cells. Rather, the evidence is overwhelming that the enhanced response was due to cooperative effects of RT with an IL-3 augmented tumorspecific immune response.…”

Section: Discussionmentioning

confidence: 85%

Tetracycline-regulated intratumoral expression of interleukin-3 enhances the efficacy of radiation therapy for murine prostate cancer

Hong

et al. 2006

Cancer Gene Ther

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The aim of this study was to investigate means of increasing the efficiency with which cancer cell death following local radiation therapy (RT) is translated into the generation of tumor immunity since, if this were to be achieved, it would be expected to enhance the rates of disease-free recurrence and survival. Our investigations centered around the use of interleukin-3 (IL-3), expressed intratumorally using an inducible adenoviral vector, to alter the immunogenicity of established murine TRAMP-C1 prostate cancer receiving a course of fractionated local RT (7 Gy per fraction per day for 5 days). Because high systemic levels of IL-3 can be associated with toxicity, a tetracycline-regulated gene delivery system was employed. The results show that while intratumoral IL-3 expression or RT alone caused a modest delay in TRAMP-C1 tumor growth, the combination was synergistic with 50% of mice being cured and developing a long-term, tumor-specific state of immunity. Immunological analyses performed on splenic lymphocytes demonstrated that, compared to RT or IL-3 alone, combined treatment significantly increased the number of tumorspecific IFN-g-secreting and cytotoxic T cells. The study demonstrates that tetracycline-regulated IL-3 gene expression within tumors can enhance the immune response to prostate cancer and this can augment the efficacy of a course of RT without additional side effects.

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Section: Discussionmentioning

confidence: 85%

Tetracycline-regulated intratumoral expression of interleukin-3 enhances the efficacy of radiation therapy for murine prostate cancer

Hong

et al. 2006

Cancer Gene Ther

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“…In recent years, interest has increased in development of combined strategy of radiotherapy and immunotherapy for treatment of established tumors [44][45][46].…”

Section: Discussionmentioning

confidence: 99%

Combined radiation therapy and dendritic cell vaccine for treating solid tumors with liver micro‐metastasis

Chen

Xia

et al. 2004

The Journal of Gene Medicine

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“…Two days after the completion of treatment, mice treated with TBI and IL-2 had significantly fewer lung tumors than mice treated with either TBI or IL-2 alone. In mice treated with TBI and IL-2, significantly more natural killer cells and macrophages were noted in the tumors, peripheral blood, and spleen compared to mice treated with either treatment alone; no differences in CD4+ or CD8+ cells were noted in mice treated with TBI and IL-2 compared to those treated with IL-2 (51). A follow-up study demonstrated that delaying the start of treatment by 3 days allowed for melanoma disease burden to double.…”

Section: Introductionmentioning

confidence: 99%

Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

Barker

Postow

2014

International Journal of Radiation Oncology*Biology*Physics

139

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Radiotherapy has long played a role in the management of melanoma. Recent advances have also demonstrated the efficacy of immunotherapy in the treatment of melanoma. Preclinical data suggest a biologic interaction between radiotherapy and immunotherapy. Several clinical studies corroborate these findings. This review will summarize the outcomes of studies reporting on patients with melanoma treated with a combination of radiotherapy and immunotherapy. Vaccine therapies often use irradiated melanoma cells, and may be enhanced by radiotherapy. The cytokines interferon-alpha and interleukin-2 have been combined with radiotherapy in several small studies, with some evidence suggesting increased toxicity and/or efficacy. Ipilimumab, a monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, has been combined with radiotherapy in several notable case studies and series. Finally, pilot studies of adoptive cell transfer have suggested radiotherapy may improve the efficacy of treatment. The review will demonstrate that the combination of radiotherapy and immunotherapy has been reported in several notable case studies, series and clinical trials. These clinical results suggest interaction and the need for further study.

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Low‐dose total body irradiation augments the therapeutic effect of interleukin‐2 in a mouse model for metastatic malignant melanoma

Cited by 18 publications

References 17 publications

Tetracycline-regulated intratumoral expression of interleukin-3 enhances the efficacy of radiation therapy for murine prostate cancer

Tetracycline-regulated intratumoral expression of interleukin-3 enhances the efficacy of radiation therapy for murine prostate cancer

Combined radiation therapy and dendritic cell vaccine for treating solid tumors with liver micro‐metastasis

Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

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