P08.02 EGFRvIII induced GBM invasion and survival is dependent upon Stat5 activation and Fn14 expression

Abstract

Abstracts iii53NEURO-ONCOLOGY • MAY 2017 given via the ommaya reservoir on day 3 and 5 to complete one cycle of the therapy. This 7-day cycle was repeated at the next week. Each two-cycle constituted one full course of therapy. The treatment consisted of two 1-week cycles of therapy over 8-12 weeks period. Side-reaction were observed, such as headache,fever,and so on. Besides side-reaction, The efficacy was assessed by MRI scans retreated at 2-or 3-month interval and the survival of the patient summarized according to the follow-up also. RESULTS: From September 2002 to May 2004, six malignant glioma patients were treated with local CIK cells therapy for ten courses, all the patients were followed up from 7 to 24 months by the end of March 2005. The Side-reaction included fever in two cases, headache in three cases and transient aphasia in one case and limb weakness in one patients, they were all controlled and the patient could tolerate. For the six patients in our study, with two out of 6 patients were still alive by the end of May 2016, survival time without recurrence was 13 and 12 years and the Karnofsky Permanence Scale were 100 and 70, respectively. Of the four patients with tumor recurrence, disease-free survival time was twenty months without other treatment after immunotherapy in one case, the rest three patients died. The efficacy was assessed: CR was in two cases;PR and ST were each in one case and PR in two cases. CONCLUSION: CIK cells can be administered intracavitary into CNS to treat primary malignant gliomas,the side-reaction was well tolerated; According to the eligibility criteria strictly, local cytokine-induced killer cell therapy for malignant gliomas appears to be safe and effective, it should be considered an option for patients with high-grade gliomas refractive to standard therapeutic approaches. INTRODUCTION: Therapies targeting T-cell inhibitory checkpoint signalling pathways are redefining cancer survival in many solid malignancies. Unfortunately only a minority of patients respond, with mounting evidence that tumour response and patient survival are significantly associated with the presence of tumour PD-L1 expression, which prevents immune activation in situ within the tumour. We hypothesised that pre-conditioning of the tumour immune microenvironment using targeted, virus-mediated interferon stimulation, would upregulate PD-L1 protein expression and improve the efficacy of sequential checkpoint blockade. Oncolytic viruses (OV) stimulate anti-tumour immunity, and represent a promising novel form of cancer immunotherapy. However almost all brain tumour studies to date administer OV via intra-lesion injection, following a largely untested belief that intravenous (IV) administration will not deliver virus to this site, due to exclusion by the blood brain barrier. MATERIALS AND METHODS: In this windowof-opportunity clinical study 9 patients were injected IV once with 1x10 10 TCID 50 of oncolytic human Orthoreovirus (reovirus) ahead of planned surgical resection of their brain tumour....