MultiCell Technologies’ portfolio encompasses a proprietary technology platform, Epitope-directed T-cell Immunotherapy (E.T.I.), which enables the delivery of disease-associated epitope peptide(s) via engineered human immunoglobulins.  An effective therapeutic is created as a result of the greatly extended pharmacokinetics of the peptide epitope, and by specific targeting of immune cells through Fc receptors binding the functional Fc domain.  ETI is an in vivo therapeutic antibody technology that does not require patient-customized processing of autologous cells prior to administration of the drug to patients.  In addition, ETI does not involve viral or cell-based vectors, and thus does not elicit the untoward immune responses associated with these vectors.

The uniqueness of the ETI platform is related to its novel epitope delivery vehicle, namely chimeric recombinant immunoglobulin G (IgG) molecules that carry the epitope sequence(s) in the hyper variable complementary determining region(s) (CDR).  The epitope sequences are introduced into the CDR region of the recombinant heavy chain by swapping out the wild type CDR sequence and inserting the epitope at the level of the cDNA expression cassette.  Once the backbone IgG heavy chain cDNA has been constructed, production of new therapeutics from this platform becomes an iterative process that differs only in inserted epitope sequences.  The resulting chimeric IgG therapeutic, or “IgP”, can be administered and marketed similarly to how currently marketed therapeutic antibodies such as Rituxan® and Herceptin® are administered and marketed.

The mechanism of action of such novel IgP therapeutic agents is very different from that of conventional antibody therapeutics, however, leveraging key positive features of both passive immunotherapy and active immunotherapy – two areas of considerable growth within the biopharmaceutical industry.

MCT-475, an IgP therapeutic agent, currently in the discovery / optimization stage, is the first of a family of prospective cancer therapeutics based on the use of our patented ETI antibody therapeutics technology in concert with our synthetic dsRNA therapeutic agent MCT-465.  MCT-475 is targeted for the treatment of cancers such as triple negative breast carcinoma.  MCT-475’s mechanism of action is more similar to that of Provenge® (active immunotherapy) than to the mechanism of action of Rituxan® and Herceptin® (passive immunotherapies).  More precisely, the mechanism of action of MCT-475 relies on the induction of potent anti-cancer immune responses through effective targeting of cancer epitopes to antigen presenting cells (APC), in conjunction with a strong stimulation of the innate immune system elicited by MCT-465.

The diagrams1 below illustrate the key synergistic and active immunotherapeutic effect between an IgP and synthetic dsRNA (MCT-465) in a mouse model.  Note the reduction of tumor size after simultaneous treatment with Ig-NP + MCT-465.

tumor_diameter_chart

Note the Active Immunotherapy properties of Ig-NP + MCT-465 such as induction of immune memory and cross-protection when mice previously treated with Ig-NP + MCT-465 are administered a second dose of tumor cells (Secondary Challenge) and exhibit no tumor growth.

primary_tumor_diameter_chart

1.  Bot A., et al., Immunologic Control of Tumors by In Vivo Fcγ Receptor-Targeted Antigen Loading in Conjunction with Double-Stranded RNA-Mediated Immune Modulation, J. Immunology, 2006, 176: 1363–1374.