WOONSOCKET, R.I., -- MultiCell Technologies, Inc. (OTCQB: MCET) is pleased to announce the acceptance by the American Society for Cell Biology (ASCB) of abstract "Short Synthetic Double Stranded RNA with Dual Activity - Oncolytic and Immune Modulatory - for Hepatocellular Carcinoma." The preclinical research results will be presented by Anand Ghanekar M.D., Ph.D., Division of Cellular & Molecular Biology, Toronto General Hospital Research Institute, at the 2012 ASCB Annual Meeting in San Francisco, CA, December 15-19, 2012.
Poster Session: Cancer Therapy II Day/Date of Presentation: Tuesday, December 18, 2012 Time of Presentation: 12:30 PM - 2:00 PM PST Place: Exhibit Halls A-C Presentation Number: 2444 Board Number: B1425
Dr. Ghanekar's research was supported by MultiCell via a sponsored research grant with the University Health Network, Toronto General Hospital Research Institute, Ontario, Canada. The research results to be presented by Dr. Ghanekar support further mechanistic and in vivo studies exploring the safety, effectiveness and utility of MCT-465 and MCT-485 as novel therapeutic agents as a treatment for hepatocellular carcinoma and other cancers.
About MCT-465 and MCT-485 MCT-465 and MCT-485 are the first of a family of prospective cancer therapeutics based on the use of our patented TLR3 signaling technology. MCT-465 and MCT 485 are in preclinical development, and are being investigated as prospective treatments for primary liver cancer and triple negative breast cancer.
The immune system is composed of two synergistic elements: the innate immune system and the adaptive immune system. Stimulation of the innate immune system through key receptors plays a critical role in triggering the adaptive immune response stimulating T and B cells to produce antibodies. In cancer, this integrated defense system does not work well, resulting in suboptimal activation of innate immunity and thus, late or inefficient adaptive immunity. The innate immune system is composed of a family of ten receptor molecules, the Toll-like Receptors (TLR1-TLR10), which act as sentries to identify invaders and signal the alarm to mobilize the body's array of immune defenses.
Within the tumor lesion, there may be infiltrating monocytes, dendritic cells and leukocytes in general, that have the capability to mobilize an adaptive or innate immune response but they are either silent or immune suppressive in the absence of select immune interventions. Such infiltrating non-cancerous immune cells may express TLR3, other TLRs, RIG-I and/or MDA-5. In addition, within tumor lesions, there may be cancerous cells or stromal cells or cancer stem cells which express TLR3, other TLRs, RIG-I and MDA-5 (representing RNA-sensing molecules).
Cancer stem cells are thought to play a role in a tumor's resistance to therapy. While significant progress has been made in developing cancer therapies that result in cytoreduction and thus tumor regression, the control of cancer over a longer interval and especially of metastatic disease, remains a key goal. Cancer stem cells are believed to be responsible for cancer relapse by being less sensitive to conventional therapies.
MultiCell 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 foreign patents and patent applications related to the isolation and differentiation of liver stem cells. The role of liver stem cells in the carcinogenic process has recently led to a new hypothesis that hepatocellular carcinoma arises by maturation arrest of liver stem cells.
Double stranded RNA (dsRNA) provides a therapeutic avenue for cancer treatment through (a) activating intra-tumoral leukocytes, abrogating their immune suppressive activity and/or (b) interacting with cancerous cells and directly inducing apoptosis, or indirectly through mobilization of immune effector mechanisms.
MCT-465 is a high molecular weight synthetic dsRNA (polyA:polyU, of 70bps) with immune enhancing properties. The mechanism of action of MCT-465 is pleiotropic and mediated by RNA sensors - such as TLR3, 7/8, MDA-5 and RIG-I - expressed by antigen presenting cells and select cases, by tumor cells:
Induction of pro-inflammatory, immune enhancing cytokines locally and systemically;
Anti-angiogenic effects through a local exposure to IL-12 / IFNgamma;
In select cases, direct pro-apoptotic anti-tumoral effect.
Prior studies with similar compounds support a strong immune enhancing effect of MCT-465, consisting in generation of Tc immunity against tumors, when administered as a companion to a vaccine. This raises the possibility that MCT-465 is an effective adjunctive therapy to any small molecule targeted therapy (such as tyrosine kinase inhibitors - TKIs) that results in release of endogenous tumor antigen while interfering minimally with the immune competence.
MCT-485 is a low molecular weight synthetic dsRNA (polyA:polyU of 5bps) with direct tumor cytolytic properties. The mechanism of action of MCT-485 is pleiotropic yet distinct from that of MCT-465:
Induction of tumor cell death upon direct exposure, while normal cells are minimally affected.
Production of TNF-alpha by cancer cells resulting in amplified tumor cell death and a localized immune reaction that has the potential to generalize and curb progression of metastatic cancer.
About MultiCell Technologies, Inc.
MultiCell Technologies, Inc. is a clinical-stage biopharmaceutical company developing novel therapeutics and discovery tools that address unmet medical needs for the treatment of neurological disorders, hepatic disease and cancer. For more information about MultiCell Technologies, please visit http://www.multicelltech.com
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