RXi's approach to immunotherapy builds on well-established methodologies of adoptive cell transfer. Immune cells, such as T-lymphocytes are isolated from specific patients or retrieved from allogeneic immune cell banks, and then expanded and possibly processed to express tumor-binding receptors.
Our method introduces a new and important step in ex-vivo processing of the immune cells. This step eliminates the expression of immunosuppressive receptors or proteins from the therapeutic immune cells, making them less sensitive to tumor resistance mechanisms and thus improving their ability to destroy the tumor cells.
Our process involves ex-vivo treatment of the immune cells with oligonucleotides inhibiting expression of immune checkpoint genes. To achieve the suppression of gene activity, oligonucleotides need to be delivered inside target cells. The transfection of immune cells with oligonucleotides is technically challenging. Commonly used methods, such as lipid-mediated transfection and electroporation are of low efficiency and associated with high cell toxicity.
Our self-deliverable RNAi (sd-rxRNA) technology* provides an efficient way of transfecting short oligonucleotides in immune cells. The technology can be combined with a variety of cell processing protocols used in clinical practice.
sd-rxRNA for virtually any target can be easily generated in a short period of time. MirImmune uses a proprietary algorithm yielding a series of sd-rxRNA compounds with high knock-down efficiency. The most active compounds can be validated within several months and selected for subsequent preclinical and clinical development.
Our approach provides some key advantages over combinations of immunotherapeutic treatments:
- For each treatment, we create a single therapeutic agent – activated immune cells modified by oligonucleotides – in which multiple immune checkpoints are attenuated.
- The therapeutic immune cells lack side effects associated with the checkpoint inhibitor toxicity, while potentially providing efficacy similar to combination treatments.
- Our streamlined discovery and development combined with the ease of manufacturing offer unprecedented opportunities for targeting novel immune checkpoints in a variety of cell-based immunotherapies.