MCT-465
Until recently, the discovery and development of cancer immunotherapies was focused on finding and expanding the portfolio of target antigens expressed on the membrane of cancer cells. That strategy led to therapeutic monoclonal antibody blockbuster drugs such as Avastin®, Rituxan® and Herceptin®. With the recent approval of Provenge® for the treatment of hormone refractory prostate cancer, the era of FDA approved drugs that stimulate a patient’s immune system against cancerous cells has begun. Drugs that stimulate a patient’s immune system against cancerous cells is called “Active Immunotherapy”.
We now know that 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.
MultiCell’s therapeutic development efforts and intellectual property in the field of cancer immunotherapy has resulted in active immunotherapy investigational agents that achieve specific control of the immune system at two levels: the innate immune system and the adaptive immune system.
MCT-465
Active immunotherapy investigational agents resulted from an exciting discovery leading to a proprietary platform based on immunomodulatory double stranded ribonucleic acid (dsRNA) technology. Initially, MultiCell’s scientists discovered a method to greatly improve the therapeutic index (pharmacological effect/toxicity) of synthetic dsRNA by size fractionation of the synthetic material or design of a dsRNA of a pre-defined size. This method – leveraging widely different biological effects of various synthetic RNAs – yielded multiple investigational agents with defined molecular size and biological properties.
MCT-465 is a high molecular weight dsRNA of defined size and chemical composition, and is obtained by synthetic chemistry.
The postulated mechanism of action (see Diagram) and biochemical properties of MCT-465 are:
- Induction of immune cytokines such as IL-12 through transcriptional and translational control of key signaling pathways that emanate from RNA sensing molecules such as TLR, RIG-I and MDA-5. This type of induction ensures deployment of a type one T cell response desired in oncology indications. In addition, through IL-12 – IFN induction it has an anti-angiogenic effect exploitable in cancer and other disease indications, leading to a multi-pronged mechanism against cancer – an important competitive advantage.
- Decreased production of TNF-alpha, responsible for the acute toxic effect of conventional dsRNA formulations encompassing a wide range of molecular sizes, when delivered systemically. Other dsRNA formulations elicit high levels of cytotoxic TNF-alpha production, consistent with the suboptimal therapeutic index observed in the clinic.
- Decreased direct cellular cytotoxicity, resulting in additional increase of therapeutic index; and,
- Retained pro-apoptotic capabilities in target receptor (TLR) positive cancer cells.
MCT-465 is thought to be a more potent yet safer active immunotherapy exhibiting a multi-pronged mechanism of action that could be utilized alone or together with other treatments to effectively control cancer through immunity. It is expected that MCT-465, at maximal tolerated dose, will retain its pharmacological potency while offering the most therapeutic benefit. MCT-465 could also enable a patient’s immune system to respond against endogenous tumor antigens; or together with co-administered antigens, MCT-465 could promote induction of broad and effective immunity against cancerous cells.
