CAR-T Cell Therapy: Just the First Step for Immuno-Oncology

(DGIwire) – The U.S. Food and Drug Administration’s recent approval of Novartis’ gene therapy—for the treatment of children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia—represents a watershed moment for healthcare. As Healio recently reported, Kymriah provides unprecedented benefits to poor prognosis patients who have exhausted all other treatment options.

What makes this treatment—the first gene therapy available in the U.S.—so interesting is that it is a form of adoptive cell transfer known as chimeric antigen receptor (CAR) T-cell therapy. According to the National Cancer Institute, this requires drawing blood from patients and separating the T (immune) cells. Using a disarmed virus, the T cells are then genetically engineered to produce CARs. These receptors allow the T cells to recognize and attach to a specific protein, or antigen, on tumor cells. Once the collected T cells have been engineered to express the antigen-specific CAR, they are expanded in the lab into the hundreds of millions. The final step is infusing the cells into the patient, where they multiply, recognize and kill cancer cells that harbor the antigen on their surfaces.

“Recent milestones in CAR-T therapy are inspiring other lines of research within the field of immuno-oncology,” says Dr. Geert Cauwenbergh, President and CEO of RXi Pharmaceuticals, a clinical-stage RNAi company developing therapeutics based on its proprietary self-delivering RNAi (sd-rxRNA®) platform. “One such approach involves siRNA compounds.”

The company has developed a process involving ex-vivo treatment of the immune cells with siRNA compounds 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. In addition, studies conducted by RXi, demonstrate robust cellular uptake in a number of immune effector cells with little to no cell loss. The technology can be combined with a variety of cell processing protocols currently used in clinical practice, as well as other cell based therapies such as CAR T-cell therapy.

sd-rxRNA compounds can 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 adoptive cell transfer with immune checkpoint blocking antibodies.

“The potential of this type of therapy is very promising and exciting in the context of current advancements within immuno-oncology,” Dr. Cauwenbergh adds.