Targeting CD133+ of Cancer Stem Cells by Oncolytic Viruses

Track Code: 
13KU047M
Summary: 

Using the mutated version of herpes simplex virus-1 (HSV1) to target and terminate CD133+ cancer stem cells.

Overview: 

While the CD133+ marker of cancer stem cells (CSCs) has long been of interest in cancer treatment due to its expression in a multitude of cancers, it has remained out of reach until now because there was no way to effectively target it. In response, Dr. Farassati and his collaborators developed the first ever version of an oncolytic virus targeted against CD133+ cells.

CSCs provide tumors with enhanced resistance to anti-cancer therapies and are considered to be responsible for the eventual recovery and regrowth of tumors after treatment. They are also considered to be resistant to apoptosis, resulting in tumors refractory to conventional cancer treatment. An agent with the capability of targeting CSCs, such as the virus generated in Dr. Farassati's lab, therefore will be a highly attractive tool for cancer therapy. This virus is called as Signal-Smart 2 or SS2 virus. His therapeutic virus developed by Dr. Farassati and his collaborators is a mutant version of HSV-1. The mutant showed specificity and potency against CD133+ cells in models of hepatocellular carcinoma, colorectal cancer and melanoma resulting in cancer cells' loss of viability and invasiveness and in-vivo tumor growth. The virus showed robust inhibition of tumor growth in both preventive and therapeutic in-vivo mouse models.

Applications: 

A series of major human cancer fall within target range for this strategy including: hepatocellular carcinoma, colorectal cancer, melanoma, brain tumors and pancreatic cancer.

How it works: 

Testing showed that cancers with a higher fraction of CD133+ cells were significantly more permissive to the SS2 virus as compared with cells with lower percentage of CD133+ subpopulation. Parental HSV-1, in comparison, lacked the capability to differentiate between high and low CD133+ cells and caused comparable infection in both.

Non-CD133+ expressing cell, such as majority of normal cells, were largely unaffected by SS2 while high-CD133+ expressing cancerous cells experienced significant loss of viability, invasiveness and proliferative ability 3 - 6 days post-infection with SS2.

Benefits: 

Dr. Farassati has developed the first-ever method of targeting and inhibiting the CD133+ marker of cancer stem cells - a relatively well-validated, high-potential target in cancer therapy that has been unexploited to date because no targeting methods existed prior to this development - using transcriptionally targeted HSV-1 virus.

Why it is better: 

CD133+ is over expressed in a multitude of cancers, making it an extremely compelling and novel target. Dr. Farassati's method of targeting CD133+ is both highly specific and highly lethal to CD133+ expressing CSCs.

Other Applications: 

Other relevant cancers include glioblastomas, medulloblastomas, prostate, and peripheral nerve sheath tumors.

Licensing Associate: 
Aswini Betha, PhD · abetha@ku.edu · 913-588-5713
Subcategory(s): 
Keyword(s): 
Inventor(s): 
Faris Farassati
Patent(s): 
Status: 
Patent-Pending