TSA treatment enhances apoptosis and immune gene expression on melanoma cells and TSA-treated vaccines generate immunity

<p><b>Copyright information:</b></p><p>Taken from "An epigenetic vaccine model active in the prevention and treatment of melanoma"</p><p>http://www.translational-medicine.com/content/5/1/64</p><p>Journal of Translational Medicine 2007;5():64-64.</p><p>Published online 10 Dec 2007</p><p>PMCID:PMC2231344.</p><p></p> ) B16 cells were stained with mAb, isotype controls and annexinV after treatment with TSA and analyzed by flow cytometry for the expression of MHC class I, class II, CD80, CD86 and CD40. Isotype controls are shown as shaded peaks and heavy lines represent expression determined by specific mAb staining. Values indicated in the histograms are the percent of cells positive for the respective mAb relative to the isotype staining. The data presented here are representative of more than three independent experiments. ) Kaplan-Meier plot of B6 mice (10 in each group) inoculated with TSA-treated (500 nM for 48 h) or untreated B16 cells in the trunk. ) Durable immunity in 100% of the immune animals. Tumor-free mice, 40 days after vaccination with TSA-treated B16, were re-challenged with untreated B16 cells and observed for another 60 days. The number of tumor-free mice compared to total numbers used in each treatment group is shown in parentheses

TSA-treated B16 vaccine elicits cytotoxic and IFN-γ-producing lymphocytes and requires T and NK cells in immunity

<p><b>Copyright information:</b></p><p>Taken from "An epigenetic vaccine model active in the prevention and treatment of melanoma"</p><p>http://www.translational-medicine.com/content/5/1/64</p><p>Journal of Translational Medicine 2007;5():64-64.</p><p>Published online 10 Dec 2007</p><p>PMCID:PMC2231344.</p><p></p> ) T-cell-enriched splenic lymphocytes isolated from immune or control mice after in vitro re-stimulation were analyzed in triplicate for cytotoxic activity using Cr-labeled untreated B16 or EL4 as targets. ) Splenocytes isolated from immune, B16 tumor-bearing or naive B6 mice were cultured in anti-IFN-γ coated plates with B16 cell lysate or melanoma antigen mgp100peptide and IFN-γ secretion was detected by ELISpot assay. *

Prevention and treatment of melanoma by TSA-treated (irradiated) tumor cell vaccine

<p><b>Copyright information:</b></p><p>Taken from "An epigenetic vaccine model active in the prevention and treatment of melanoma"</p><p>http://www.translational-medicine.com/content/5/1/64</p><p>Journal of Translational Medicine 2007;5():64-64.</p><p>Published online 10 Dec 2007</p><p>PMCID:PMC2231344.</p><p></p> ) Vaccination with TSA-treated (500 nM for 48 h) and irradiated (2000 Gy) B16 cells prevents B16 tumor generation. Three weeks after s.c. inoculation of TSA-treated [TSA-radiation] or untreated [radiation] B16 (1 × 10) cells in B6 mice (16 in each group); all tumor-free mice were challenged s.c. with wild type B16 (1 × 10) cells and observed for 40 days. Percentage of tumor-free mice is presented in the Kaplan-Meier plot. ) Suppression of primary tumor growth by TSA-treated and irradiated melanoma vaccine. Groups of B6 mice bearing palpable B16 (5 days tumor growth) were treated s.c. with TSA-treated and irradiated B16 [TSA-radiation] or untreated irradiated B16 (1 × 10cells) [radiation] in the opposite side of the trunk. A group of tumor-bearing mice did not receive any treatment [no treatment]. The number of tumor-free mice compared to total numbers used in each group is shown in parentheses at 42 days after treatment. ) Induction of long-term immunity in tumor-bearing mice treated with epigenetically altered melanoma vaccine. B16 tumor-bearing mice that became tumor-free following vaccine treatment were re-challenged s.c. with wild type B16 (1 × 10cells). Kaplan-Meier plot shows tumor-free survival of mice in both TSA-radiation and radiation groups after re-challenge