**Author details**

*8.3.3. Oncolytic NDV*

(Csatary, Gosztonyi et al. 2004).

involving reovirus are currently underway.

206 Tumors of the Central Nervous System – Primary and Secondary

lymphocytes (Barzon, Zanusso et al. 2006).

**9. Conclusion**

*8.3.2. Oncolytic reoviruses*

**8.4. Gene immunotherapy**

NDV is an avian paramyxovirus, which does not harm humans except for rare pulmonary infection in poultry farmers; certain strains harm neoplastic cells via a currently unknown mechanism (Reichard, Lorence et al. 1992). Interestingly, NDV also has pleiotropic immunemodulatory properties (Schirrmacher, Haas et al. 1999). It should be noted that treatment with NDV necessitates starting at a low dose as there have been examples of treatment-related death with *NDV PV701 and solid cancers* (Pecora, Rizvi et al. 2002). *MTH-68/H*, a live attenuated oncolytic viral strain of NDV, has shown promising results is a small number of GBM patients

Reovirus is a double-stranded RNA-containing virus that replicates in GBM cells because of a hyperactive ras signaling; it distinctively does not replicate in normal brain cells. A phase I clinical trial of intrattumoral administration of genetically unmodified virus was well tolerated by patients with recurrent malignant gliomas (Forsyth, Roldan et al. 2008). Further studies

Treatment of gliomas with immune therapy is based on harnessing of the patient's T-Cell mediated response to tumor cells. Typically, gene-immune therapy falls into the category of priming in the brain by the transfer of cytokine genes, like IL-2, IL-4, IL-12, and interferons gamma and beta (Freeman, Abboud et al. 1993; Borden, Lindner et al. 2000; Candolfi, Xiong et al. 2010; Denbo, Williams et al. 2011; Ryu, Park et al. 2011; Markert, Cody et al. 2012). A phase I clinical trial of the injection of cationic liposomes carrying the human IFN-Beta gene into the postsurgical cavity showed low toxicity (Wakabayashi, Natsume et al. 2008). A phase 1 trial of adenovirus-mediated gene transfer of INF-Beta was also well tolerated (Chiocca, Smith et al. 2008). Furthermore, a small pilot study of liposomal-mediated IFN-Beta gene transfer into the postsurgical cavity showed promising results (Yoshida, Mizuno et al. 2004).

Another important strategy combines cytokine gene transfer (human IL-2) paired with HSV-TK/GCV treatment (Palu, Cavaggioni et al. 1999; Colombo, Barzon et al. 2005). The results are promising in a small number of patients (Colombo, Barzon et al. 2005); in particular, biopsy following treatment showed tumor necrosis at site of administration as well as significant immune response in the form of activated cytotoxic T cells, macrophages and T-Helper/inducer

The aforementioned negative results of several key phase III clinical trials in GBM demonstrate that current proof of efficacy in preclinical models is a necessary but not sufficient condition Paula Province, Alexis Bashinski Shaefer, Benjamin McCullough and Hassan M Fathallah-Shaykh

The University of Alabama at Birmingham, Birmingham, Alabama, USA
