Jonathan Axelrod, PhD, and Eithan Galun, MD, The Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital.
Background
A number of gene therapies have entered late stage clinical trials since year 2000. Innovative gene therapy technology may have several potential benefits over the conventional drugs, such as activity in the target region only, causing lower side effects and a better efficacy in the target tissue. The utility of lytic viruses as anti-neoplastic agents has been studied for more than five decades. Recently this has included the development of engineered viruses for the delivery of therapeutic payloads to enhance killing specificity and efficiency, or to stimulate immune mediated anti-tumor activity.
We suggest new therapeutic agents of adenoviral vectors encoding IL- 6/sIL-6R fusion protein (HIL-6) for treating cancers of various types.
Market
In 2004, the global anticancer drug market exceeded $23 billion. Revenues ranged from a few million dollars for some brands all the way to almost $3 billion for Rituxan/MabThera. Global sales of 9 cancer drugs exceeded $1 billion in 2004. New classes of oncology drugs are emerging which are providing the source of strong sales growth for the biotechnology and pharmaceutical industries. Today, just under half of all the drugs now in development are cancer-related. The growth rate of anticancer drugs in the next decade is being forecasted to be two digits.
The Innovation
We developed an oncolytic recombinant adenoviral vector encoding an IL-6/sIL-6R fusion protein whose “smart” expression is regulated either: by a constitutive promoter, by a promoter enabling tumor specific expression of the transgene, by a promoter controlled by the administration of exogenous substances, or by a combination of the above methods.
This “smart” expression of the complex (IL-6/sIL-6R fusion protein) can be used for selective attacking and killing of tumor cells in patients. Furthermore, the production of the therapeutic complex by the tumor cells may also enhance additional immune cell response to the tumor site and therefore increase the immune mediated tumor rejection.
We found that our adenoviral vector, which encodes an IL-6/sIL-6R fusion protein (Hyper-IL-6), is able:
1) to successfully replicate in the target cells
2) to produce cytotoxic effects, and
3) to kill tumor cells such as hepatocellular carcinoma tumor cell lines.
This in contrary to control viruses, which did not produce infectious particles as a result of the primary infection of the target cells.
R&D Program
- Producing additional vectors.
- In-vitro tests for efficacy determination of the developed vectors in various cell types, including tumor cell lines originating from liver, bladder, breast, prostate, melanoma and colon cancers.
- Pre-clinical tests in animal models for various types of cancer including: elimination of tumor implants in mouse models and using the vectors to the treatment of endogenously induced tumors in animal.
- Efficacy and toxicity tests in order to prepare a request for clinical trial.
Contact
Yuval Kupitz,
Business Development, Pharmaceuticals
Tel: +972-2-6778364
Email: yuvalk@hadasit.co.il
