MultiCell Technologies, Inc.,a clinical-stage biopharmaceutical company, has filed a US provisional patent application concerning composition of matter, biological targets, mechanism of action, methods and formulations to achieve targeted tumour cell death.

This patent application describes a novel class of very small noncoding double stranded RNA molecules (VSRNAs) which interfere with the basic homoeostatic cellular processes in tumour cells. VSRNAs are of molecular size less than 10 bps, yet are surprisingly capable in their ability to affect the metabolism, viability and proliferative rate of tumour cells consistent with a mechanism of action that bypasses completely, or in part, the canonical known pathways and steps of RNA recognition and RNA interference.  

In contrast to other species of RNAs, VSRNAs can induce cell death through pyroptosis; a specific biological process that also involves pro-inflammatory cytokine production.  Pyroptosis results from the capability of VSRNAs to suppress or modify the amount of mRNA expressing various endogenous genes linked to the metabolism, proliferation and viability of cells, thus inducing a state of cellular stress that results in deployment of mediators of innate immunity.  VSRNAs described in this Application exert a preferential biological activity on certain tumour cells while showing no effect on normal, non-transformed cells.  

Since cancer cells are highly metabolically active, they are more reliant on key housekeeping molecules for survival as opposed to normal cells.  Through mobilization of stress pathways and non-canonical RNA sensors, VSRNAs have demonstrated the capability of activating the NF-kB pathway and Ca2+ release, resulting in (1) secretion of pre-formed cytokines stored in cell vesicles, and (2) de novo synthesis of cytokines and chemokines.  VSRNAs can be formulated, attached or integrated within delivery vehicles that target or express selectively their payload in desired cell types resulting in both immediate and long-term therapeutic effects against cancer.

MultiCell is evaluating MCT-485, a VSRNA, in animal models of hepatocellular carcinoma.  Hepatocellular carcinoma is the most common form of primary liver cancer, and is a leading cause of cancer death worldwide.  Over 1 million cases of hepatocellular carcinoma are reported annually.  Current approaches for treatment of hepatocellular carcinoma are of limited efficacy.  MCT-485, possessing both oncolytic and immune activating properties, could be superior to currently marketed therapies by providing a more robust activation of immunity, and a more global and longer lasting anti-tumour effect.  Additionally, due to its unique mechanism of action, MCT-485 could prove effective in killing other types of cancers.  MultiCell plans to initiate similar studies in relevant in vitro and animal models for other major cancers.

MultiCell Technologies' MCT-485 is a very small noncoding double stranded RNA (VSRNA), and the first of a family of prospective cancer therapeutics.  MultiCell owns rights to several issued US and foreign patents and patent applications related to MCT-485 and other RNAs.

MultiCell Technologies, Inc. is a clinical-stage biopharmaceutical company developing novel therapeutics and discovery tools for the treatment of neurological disorders, hepatic disease and cancer.