Sharply discordant biological properties of synthetic noncoding

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Triple Negative Breast Cancer | Cancer Stem Cells & Primary Liver Cancer

MultiCell Technologies has a portfolio of novel therapeutic candidates in various stages of discovery and development targeting the treatment of cancer. Specifically, MultiCell is pursuing therapies for the treatment of certain types of breast and liver cancer.

Triple Negative Breast Cancer

Breast cancer is not one disease, but many different forms of cancer all originating in the breast. According to the National Cancer Institute (NCI), in the USA in 2009 there were greater than 190,000 cases of breast cancer, and over 40,000 deaths as a result of breast cancer. The most successful recently developed treatments for breast cancer target three receptors: estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2/neu). When present in the tumor, interfering with the receptor’s ability to stimulate the growth of breast cancer cells is an effective treatment approach. For example, Herceptin®, a drug that blocks the HER2/neu receptor, had worldwide sales of $4.7 billion in 2008.

Breast cancer is usually characterized based upon the presence of, or absence of, the ER, PR and HER2/neu receptors. A “triple negative” breast cancer diagnosis means that the offending tumor lacks these receptors [estrogen receptor-negative (ER-), progesterone receptor-negative (PR-) and HER2 receptor-negative (HER2/neu-)]. Depending on the stage of its diagnosis, triple negative breast cancer can be particularly aggressive, and is more likely to recur and is less sensitive to current treatments than other forms of breast cancer.

Despite significant advances in the targeted therapy of breast carcinoma – with development and approval of biomolecules such as Herceptin® and Avastin® or small molecules that inhibit tyrosine kinases or PARP – the treatment of triple negative breast cancer remains an unmet medical need. MultiCell is pursuing the development of therapeutic candidates for the treatment of triple negative breast cancer.

Synthetic dsRNA act through mobilizing the immunity against endogenous tumor antigens (not unlike biological response modifiers such as Ipilimumab®); however, MultiCell’s dsRNA therapeutic candidates – a high molecular weight immune enhancer (MCT-465), and a low molecular weight cytolytic agent (MCT-485) – present several advantages over other agents in development or approved namely, simplicity of manufacturing and reduced cost of goods, potent immune enhancing properties, and a more favorable safety profile. Additionally, MultiCell’s immunoglobulin platform in conjunction with MCT-465 offers a unique possibility to design and develop very specific immune targeted agents against molecules important to the pathogenesis of triple negative breast carcinoma.

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Cancer Stem Cells and Primary Liver Cancer

Tumor tissues are composed of a mixture of cells with some cancer cells exhibiting stem cell-like properties (cancer stem cells). Cancer stem cells are thought to play a role in a tumor’s resistance to therapy and mediate disease relapse, progression or metastasis. While significant progress has been made in developing cancer therapies that result in tumor regression, the control of cancer over a longer interval and especially of metastatic disease, remains a key goal.

Primary liver cancer, or hepatocellular carcinoma, begins in the cells of the liver itself, whereas metastatic liver cancer is cancer that begins in other parts of the body and spreads to the liver. According to the NCI, in 2008 there were approximately 21,400 new cases of primary liver cancer and intrahepatic bile duct cancer in the United States, and approximately 18,400 (86%) of those cases resulted in death in the first 18 months after diagnosis. Hepatocellular carcinoma, frequently accompanying Hepatitis B and Hepatitis C infection, is the most common cancer in some parts of the world, with more than 1 million new cases diagnosed each year. The NCI also reports that hepatocellular carcinoma is associated with cirrhosis of the liver in 50% to 80% of patients.

The role liver stem cells play in the carcinogenic process of primary liver cancer has recently led to a new hypothesis that hepatocellular carcinoma arises by maturation arrest of liver stem cells. Cancer stem cells are believed to be responsible for cancer relapse by being less sensitive to conventional therapies and thus, offer a unique opportunity to identify and develop a new generation of more effective anticancer agents (both small molecule therapeutics and biotherapies). MultiCell Technologies owns exclusive rights to two issued U.S. patents (6,872,389 and 6,129,911), one U.S. patent application (U.S. 2006/0019387A1), and several corresponding issued and pending patents and patent applications related to the isolation and differentation of liver stem cells. MultiCell is developing therapeutic product opportunities based on the concept of targeting cancer stem cells for the treatment of hepatocellular carcinoma and intrahepatic bile duct cancer.

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