A Novel Oncolytic Herpes Capable of Cell-Specific Transcriptional Targeting of CD133± Cancer Cells Induces Significant Tumor Regression. (17th July 2018)

• Record Type: Journal Article
• Authors: Terai, Kaoru; Bi, Danse; Liu, Zhengian; Kimura, Kyle; Sanaat, Zohreh; Dolatkhah, Roya; Soleimani, Mina; Jones, Christopher; Bright, Allison; Esfandyari, Tuba; Farassati, Faris
• Is Part Of: Stem cells. Volume 36:Number 8(2018)
• Page Start: 1154
• Page End: 1169
• Publication Date: 2018-07-17
• Subjects: Cancer stem cells -- Oncolytic viruses -- CD133 -- Herpes simplex virus-1 -- Melanoma -- Colorectal cancer -- Hepatocellular carcinoma -- Liver cancer -- Therapy; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2835
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract : The topic of cancer stem cells (CSCs) is of significant importance due to its implications in our understanding of the tumor biology as well as the development of novel cancer therapeutics. However, the question of whether targeting CSCs can hamper the growth of tumors remains mainly unanswered due to the lack of specific agents for this purpose. To address this issue, we have developed the first mutated version of herpes simplex virus-1 that is transcriptionally targeted against CD133+ cells. CD133 has been portrayed as one of the most important markers in CSCs involved in the biology of a number of human cancers, including liver, brain, colon, skin, and pancreas. The virus developed in this work, Signal-Smart 2, showed specificity against CD133+ cells in three different models (hepatocellular carcinoma, colorectal cancer, and melanoma) resulting in a loss of viability and invasiveness of cancer cells. Additionally, the virus showed robust inhibitory activity against in vivo tumor growth in both preventive and therapeutic mouse models as well as orthotopic model highly relevant to potential clinical application of this virus. Therefore, we conclude that targeting CD133+ CSCs has the potential to be pursued as a novel strategy against cancer. Abstract : Cancer stem cells (CSCs) that express CD133 are considered as the primary targets for the SS2 virus (step 1). Once SS2 virus targets CD133+ CSCs leading to their destruction (steps 2–3), differentiated cancer cells are left (step 4) which expire after completion of their life-cycle resulting in a significant tumor regression (step 5).