Delivering Another Option in Immunotherapy Treatment


By Staff Reports

(DGIwire) – Within the realm of cancer care, immunotherapy is increasingly occupying the spotlight. And with good reason: as many recent headlines show, this form of therapy holds great promise for improved treatment of a wide variety of cancers. There exist several approaches to immunotherapy, each with its specific strengths.

One fascinating approach to immunotherapy, developed by RXi Pharmaceuticals, builds on well-established methodologies of adoptive cell transfer (ACT). In this approach, immune cells, such as T-lymphocytes, are isolated from a patient 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,” says Dr. Alexey Eliseev, Chief Business Officer of RXi Pharmaceuticals. “This step reduces the expression of immunosuppressive receptors or proteins on the therapeutic immune cells, making them less sensitive to tumor resistance mechanisms and thus improving their ability to destroy the tumor cells.”

The company’s process involves ex-vivo treatment of the immune cells with small RNA molecules inhibiting expression of immune checkpoint genes. To achieve the suppression of gene activity, the molecules need to be delivered inside target cells, which is technically challenging with many researchers not succeeding in this area so far. Commonly used methods, such as lipid-mediated transfection and electroporation, may be of low efficiency and may be associated with high cell toxicity.

RXi’s self-delivering RNAi (sd-rxRNA®) technology incorporates delivery properties that allow the compounds to efficiently transfect immune cells. The technology can be combined with a variety of cell processing protocols used in clinical practice.

sd-rxRNA can easily be generated within a short period of time for virtually any target in the genome. RXi 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.

This approach provides some key advantages over combinations of immunotherapeutic treatments, such as the use of ACT with immune checkpoint blocking antibodies. For each treatment, RXi will create a single therapeutic agent—activated immune cells modified by RNA—in which multiple immune checkpoints are attenuated. Since checkpoint inhibition is achieved without the use of antibodies, the use of sd-rxRNA modified therapeutic immune cells lacks some of the side effects typically associated with antibody treatments, while potentially providing similar efficacy.

“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,” Dr. Eliseev adds.

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