Maintaining and Loading Neural Stem Cells for Delivery of Oncolytic Adenovirus to Brain Tumors
Despite recent advancements in the treatment of cancer, the prognosis for patients with malignant brain tumors remains poor. The success of currently available therapies has been limited in part because of the disseminated nature of these tumors. Furtherm
- PDF / 129,236 Bytes
- 13 Pages / 504.57 x 720 pts Page_size
- 41 Downloads / 180 Views
1. Introduction 1.1. Oncolytic Virus
Cancer is a multistage genetic disease that involves alterations in multiple molecular pathways related to growth control and cell death (1). There are many genes that have been identified in recent years, which could be potential targets for novel cancer therapy.
David H. Kirn et al. (eds.), Oncolytic Viruses: Methods and Protocols, Methods in Molecular Biology, vol. 797, DOI 10.1007/978-1-61779-340-0_8, © Springer Science+Business Media, LLC 2012
97
98
A.U. Ahmed et al.
The new knowledge of the molecular mechanisms underlying oncogenesis and the development of the viral vector as a vehicle for gene delivery have permitted the formulation of the concept of cancer gene therapy. Strategies for cancer gene therapy adopt ideas and technologies ranging from generating the immune response against tumor antigens to directly attacking tumor cells. However, the therapeutic efficacy of most of the cancer gene therapy approaches is significantly compromised by the inability of the current viral vectors to deliver genes in vivo and target systemic metastasis. To overcome this problem, researchers have used the viruses’ ability to spread from their site of infection to the neighboring cells. Infected cells are killed, as they become the factories for producing the new infectious viral particles (VPs). The process of infection is particularly attractive to cancer gene therapy because it not only amplifies therapeutic genes in a tumor-selective manner, but also has the potential to lyse and kill the infected tumor cells. The use of replicating viruses against cancer, also referred to as virotherapy, has a long history that began in the early 1900s with the anecdotal reports of temporary cancer remissions in patients who received a viral immunization or had a natural viral infection (2). The success of this approach depends on our ability to identify and engineer viruses that replicate specifically in tumor cells, but not in the normal cells. These viruses, termed oncolytic viruses, are essentially tumor-specific, self-replicating, lysis-inducing cancer killers. Many oncolytic viruses that belong to several viral families have been identified or engineered. They include herpes simplex viruses, adenovirus, retroviruses paramyxoviruses, and poxviruses (3). These viruses can be categorized into four major groups on the basis of their oncolytic restriction: (1) mutation/deletionderived viruses, (2) transcriptionally targeted oncolytic viruses, (3) transductionally targeted oncolytic viruses, and (4) “naturally smart” viruses. Oncolytic viruses for cancer exploit the difference of the molecular makeup between the tumor cells and their normal counterparts; they also utilize recombinant DNA technology to engineer viral vectors to selectively replicate in the tumor cells and destroy them. 1.2. Oncolytic Viral Therapy for Malignant Glioma
Despite recent advancement in surgical techniques and adjuvant radio- and chemotherapy, the median survival for patients with GBM is approximately 12–15 months and it
Data Loading...
