3 Challenges Facing Immunotherapy and How RNAi Might Help

By Staff Reports

(DGwire) – The battle against solid tumors in cancer immunotherapy is engaging some of the brightest minds in medicine. While predictions suggest the immunotherapy market will be worth about $25 billion by 2030, there are still some hurdles to overcome in the effort to improve treatment options, including:

  • Boosting the immune system to fight: As reported in National Reviews of Cancer, boosting a patient’s immune system to fight cancer cells is difficult due to the variety of receptors on the surfaces of immune cells, called immune checkpoints, which inhibit attacks on tumor cells. Although there has been some success in targeting checkpoints like PD-1 and blocking them, it can be hard to harness antibodies to target multiple checkpoints at once. However, there are some companies working to address this challenge. For example, RXi Pharmaceuticals is working on a new technology that may be able to target multiple immunosuppression pathways in a single therapeutic entity, providing a significant advantage over an antibody approach. Called self-delivering RNAi (sd-rxRNA®), it incorporates drug-like properties into an RNAi compound allowing for an efficient delivery in various immune effector cells. After cell delivery, the double-stranded RNA molecules interfere with the expression of targeted genes. The company is developing two proprietary sd-rxRNA® compounds, RXI-762 and RXI-804, which are designed to target checkpoints known as PD-1 and TIGIT, respectively, in immune cells.
  • Preserving T cells’ properties: In addition to checkpoint inhibition, Nature Medicinenotes that developing an effective immunotherapy that preserves some of T cells’ other important properties, such as their differentiation and persistence, may improve anti-tumor efficacy. “We believe that sd-rxRNA® is the ideal technology to also affect cell differentiation to enhance T cells’ long-term survival and ‘metabolic fitness,’” says Geert Cauwenbergh, Dr.Med.Sc., President and CEO of RXi Pharmaceuticals.
  • Battling the unique nature of solid tumors: Positive results have come from using adoptive cell transfer (ACT) in cancer treatment. ACT involves extracting, expanding and reinfusing T cells into a patient’s body in order to get those cells to fight cancer. New ACT developments such as CAR T-cell therapy—using engineered cells—have been successful in hematologic cancers, but it has been realized that solid tumors respond differently to CAR therapy than hematologic ones, reports Cell Research. “Our sd-rxRNA technology is ideally suited for use with several forms of ACT, and allows for the combined use of checkpoint inhibition and cell differentiation targets. This may open avenues for making ACT more effective in more cancer types, including solid tumors,” notes Dr. Cauwenbergh.

“The potential rewards for an effective immuno-oncology therapy are substantial, and researchers are continually looking for new strategies,” Dr. Cauwenbergh adds. “We believe sd-rxRNA® has inherent advantages over other approaches that have been tried, such as antibodies and gene editing, and represents the best RNAi technology for ACT. Safety, efficacy and long-term effects have been demonstrated in a variety of in vivo and in vitro cancer models, and safety and efficacy have been proven in clinical studies by direct injection. The future prospects of this field are exciting indeed.”

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