Targeted Oncolytic Herpes Simplex Viruses for Aggressive Cancers

被引:7
作者
Wong, Jennifer [1 ,2 ]
Lee, Cleo [3 ]
Zhang, Kevin [4 ]
Rennie, Paul S. [4 ]
Jia, William [1 ,2 ,4 ]
机构
[1] Univ British Columbia, Dept Surg, Brain Res Ctr, Vancouver, BC V5Z 1M9, Canada
[2] Univ British Columbia, Dept Surg, Div Neurosurg, Vancouver, BC V5Z 1M9, Canada
[3] Stanford Univ, Stanford, CA 94305 USA
[4] Vancouver Gen Hosp, Prostate Res Ctr, Vancouver, BC, Canada
关键词
Herpes simplex virus type-1; TTDR-HSV; oncolytic virus; MUTANT EXPRESSING ICP34.5; STEM-CELLS; TRANSCRIPTIONAL CONTROL; REGULATORY PROTEIN; BINDING PROTEIN; MOUSE MODEL; TUMOR; GLIOMA; GENE; REPLICATION;
D O I
10.2174/138920112800958751
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Herpes simplex virus (HSV) is a well-known vector that is often used for gene therapy to treat cancers. The most attractive feature of HSV is its ability to destroy tumors through a distinctive oncolytic mechanism where the virus can destroy cancer cells via cell lysis, a killing function that no anti-cancer drugs can mimic. Importantly, HSV is a safe and effective virus that can be easily manipulated to preferentially replicate in tumor cells. In the last 20 years of reengineering efforts, a number of HSV designs, including the classical G207, have been focused on deleting viral genes in order to render the virus tumor specific. Although such designs can successfully destroy tumor xenografts in animal models, with minimal impact on normal tissues, a common trade-off is the marked attenuation of the virus. This problem is most profound in many clinical tumors, where virus dissemination is often hindered by the difficult cellular and molecular terrain of the human tumor mass. In order to harness all of HSV's replication potential to destroy tumor cells, efforts in our lab, as well as others, last several years have been focused on engineering an oncolytic HSV to target tumor cells without deleting any viral genes, and have since generated highly tumor specific viruses including our transcriptional translational dually regulated HSV (TTDR-HSV). In this review, we will discuss the improvements associated with the newer TTDR-HSV design compared to the classical defective HSV designs such as G207 and tk- HSV. Lastly, we will review additional cellular features of aggressive tumors, such as their immense cellular heterogeneity and volatility, which may serve to hinder the dissemintation of TTDR-HSV. The challenge for future studies would be to explore how TTDR-HSV could be redesigned and/or employed with combinatorial approaches to better target and destroy the heterogeneous and dynamic cell populations in the aggressive tumor mass.
引用
收藏
页码:1786 / 1794
页数:9
相关论文
共 70 条
  • [1] [Anonymous], MOL THER
  • [2] Glioma stem cells promote radioresistance by preferential activation of the DNA damage response
    Bao, Shideng
    Wu, Qiulian
    McLendon, Roger E.
    Hao, Yueling
    Shi, Qing
    Hjelmeland, Anita B.
    Dewhirst, Mark W.
    Bigner, Darell D.
    Rich, Jeremy N.
    [J]. NATURE, 2006, 444 (7120) : 756 - 760
  • [3] CD133+ and CD133- glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles
    Beier, Dagmar
    Hau, Peter
    Proescholdt, Martin
    Lohmeier, Annette
    Wischhusen, Joerg
    Oefner, Peter J.
    Aigner, Ludwig
    Brawanski, Alexander
    Bogdahn, Ulrich
    Beier, Christoph P.
    [J]. CANCER RESEARCH, 2007, 67 (09) : 4010 - 4015
  • [4] Chen R, CANC CELL, V17, P362
  • [5] ASSOCIATION OF A M(R)-90,000 PHOSPHOPROTEIN WITH PROTEIN-KINASE PKR IN CELLS EXHIBITING ENHANCED PHOSPHORYLATION OF TRANSLATION INITIATION-FACTOR EIF-2-ALPHA AND PREMATURE SHUTOFF OF PROTEIN-SYNTHESIS AFTER INFECTION WITH GAMMA(1)34.5(-) MUTANTS OF HERPES-SIMPLEX-VIRUS-1
    CHOU, J
    CHEN, JJ
    GROSS, M
    ROIZMAN, B
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (23) : 10516 - 10520
  • [6] B-myb promoter retargeting of herpes simplex virus γ34.5 gene-mediated virulence toward tumor and cycling cells
    Chung, RY
    Saeki, Y
    Chiocca, EA
    [J]. JOURNAL OF VIROLOGY, 1999, 73 (09) : 7556 - 7564
  • [7] eIF-4E expression and its role in malignancies and metastases
    De Benedetti, A
    Graff, JR
    [J]. ONCOGENE, 2004, 23 (18) : 3189 - 3199
  • [8] MicroRNA Regulation of Cancer Stem Cells and Therapeutic Implications
    DeSano, Jeffrey T.
    Xu, Liang
    [J]. AAPS JOURNAL, 2009, 11 (04): : 682 - 692
  • [9] Chemotherapy resistance of glioblastoma stem cells
    Eramo, A.
    Ricci-Vitiani, L.
    Zeuner, A.
    Pallini, R.
    Lotti, F.
    Sette, G.
    Pilozzi, E.
    Larocca, L. M.
    Peschle, C.
    De Maria, R.
    [J]. CELL DEATH AND DIFFERENTIATION, 2006, 13 (07) : 1238 - 1241
  • [10] Glioblastoma-induced attraction of endogenous neural precursor cells is associated with improved survival
    Glass, R
    Synowitz, M
    Kronenberg, G
    Walzlein, JH
    Markovic, DS
    Wang, LP
    Gast, D
    Kiwit, JRR
    Kempermann, G
    Kettenmann, H
    [J]. JOURNAL OF NEUROSCIENCE, 2005, 25 (10) : 2637 - 2646