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. 2016 Aug;24(8):1478-83.
doi: 10.1038/mt.2016.86. Epub 2016 Apr 25.

Three-year Follow up of GMCSF/bi-shRNA(furin) DNA-transfected Autologous Tumor Immunotherapy (Vigil) in Metastatic Advanced Ewing's Sarcoma

Maurizio Ghisoli  1   2   3 , Minal Barve  1   2 , Robert Mennel  2   4 , Carl Lenarsky  2   3 , Staci Horvath  1 , Gladice Wallraven  5 , Beena O Pappen  5 , Sam Whiting  5 , Donald Rao  6 , Neil Senzer  1   5 , John Nemunaitis  1   2   5   3   6
Affiliations

Three-year Follow up of GMCSF/bi-shRNA(furin) DNA-transfected Autologous Tumor Immunotherapy (Vigil) in Metastatic Advanced Ewing's Sarcoma

Maurizio Ghisoli et al. Mol Ther. 2016 Aug.

Abstract

Ewing's sarcoma is a devastating rare pediatric cancer of the bone. Intense chemotherapy temporarily controls disease in most patients at presentation but has limited effect in patients with progressive or recurrent disease. We previously described preliminary results of a novel immunotherapy, FANG (Vigil) vaccine, in which 12 advanced stage Ewing's patients were safely treated and went on to achieve a predicted immune response (IFNγ ELISPOT). We describe follow-up through year 3 of a prospective, nonrandomized study comparing an expanded group of Vigil-treated advanced disease Ewing's sarcoma patients (n = 16) with a contemporaneous group of Ewing's sarcoma patients (n = 14) not treated with Vigil. Long-term follow-up results show a survival benefit without evidence of significant toxicity (no ≥ grade 3) to Vigil when administered once monthly by intradermal injection (1 × 10e(6) cells/injection to 1 × 10e(7) cells/injection). Specifically, we report a 1-year actual survival of 73% for Vigil-treated patients compared to 23% in those not treated with Vigil. In addition, there was a 17.2-month difference in overall survival (OS; Kaplan-Meier) between the Vigil (median OS 731 days) and no Vigil patient groups (median OS 207 days). In conclusion, these results supply the rational for further testing of Vigil in advanced stage Ewing's sarcoma.

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Figures

Figure 1
Figure 1
(a) Vigil is a 5,140 bp plasmid of a bifunctional shRNA-furin DNA sequence which prevents cleavage of TGFβ precursor into functional TGFβ1 & TGFβ2 and a GMCSF DNA sequence which stimulates antigen presentation and adaptive immune response when expressed after placement by electroporation into individual autologous tumor tissue which provides the full tumor antigen (Ag) profile and has demonstrated in phase 1, 2 testing induction of circulating cytotoxic T lymphocytes capable of specific lytic activity (ELISPOT and response) to autologous tumor. (b) Vigil constructing is portrayed.
Figure 2
Figure 2
Survival from surgical procurement of advanced Ewing's patients successfully harvested for Vigil construction (n = 30). Comparison is made of those who received Vigil (n = 16) versus those who did not receive Vigil ((n = 14) as a result of construction failure or choice of other management). All patients are censored alive as of dates provided on 19 October 2015.
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