Radio Frequency Ablation Combined with Interleukin-2 Induces an Antitumor Immune Response to Renal Cell Carcinoma in a Murine Model
ABSTRACT Immune based therapy has gained renewed interest in the search for treatment strategies for metastasized renal cell carcinoma. We determined whether radio frequency ablation combined with interleukin-2 would induce a tumor specific immune response and serve as an in situ vaccine against renal cell carcinoma.
Mice with orthotopic renal tumors were treated with radio frequency ablation combined with interleukin-2, radio frequency ablation only, interleukin-2 only or no treatment as the control. Immunohistochemistry was done to determine which cells were present in the tumor after treatment. In vitro tumor specific cytotoxicity assays were performed with CD8+ T and natural killer cells derived from the spleen of treated mice. To study whether treatment could prevent metastasis or affect the growth of established metastases we induced lung metastasis intravenously before or after treatment and subsequently quantified it.
The number of natural killer, CD4+ and CD8+ T cells was significantly increased in the tumor tissue of radio frequency ablation/interleukin-2 treated mice (p <0.0001). Natural killer and CD8+ T cells showed strong antitumor activity in vitro after combination treatment. Lung metastatic formation was significantly prevented in mice that received combination therapy (p <0.0001). Lung metastases were significantly smaller after combination treatment (vs interleukin-2 p = 0.025).
Radio frequency ablation of the primary tumor combined with interleukin-2 induces a systemic antitumor immune response to renal cell carcinoma, which is much stronger than that of interleukin-2 monotherapy. This effect appears to be mediated by natural killer and CD8+ T cells. It may have an important role in the development of new immunotherapy strategies for renal cell carcinoma.
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ABSTRACT: Background: Current immunomodulatory agents for stage III and IV melanoma exert different mechanisms of action that manifest in distinct adverse events. Objective: This systematic review aims to synthesize safety data from clinical trials on ipilimumab, vemurafenib, interferon (IFN) alfa-2b, dacarbazine and interleukin (IL)-2 to elucidate the severe adverse events associated with each melanoma therapy. Methods: Through a systematic search using MEDLINE, EMBASE and the Cochrane Central Register between January 1, 2010 and June 1, 2012, we identified 32 clinical trials with 5802 subjects that met the inclusion criteria. Results: Ipilimumab was associated with immune-mediated diarrhea and colitis, with an incidence rate of 0.0017 cases per 100 person-years. Patients receiving vemurafenib developed keratoacanthomas and cutaneous squamous cell carcinoma at an incidence rate of 0.0025 cases per 100 person-years. Treatment with IFN alfa-2b precipitated depression at an incidence rate of 0.0002 cases per 100 person-years. Dacarbazine was associated with respiratory toxicity and dyspnea, with incidence rates of 0.0001 and 0.00008 cases per 100 person-years, respectively. IL-2 treatment induced vascular leak syndrome (VLS), with symptoms of hypotension and oliguria, was observed at incidence rates of 0.17 and 0.15 cases per 100 person-years, respectively. Findings may serve as a foundation for future research in this area and guide clinical recommendations.Journal of Dermatological Treatment 06/2013; 25(5). DOI:10.3109/09546634.2013.813897 · 1.67 Impact Factor