RXi Pharmaceuticals, a biotechnology company developing the next generation of immuno-oncology therapeutics based on its proprietary self-delivering therapeutic platform, has entered into a research collaboration with the Karolinska Institutet in Stockholm, Sweden. This collaboration will explore RXi’s sd-rxRNA compounds against targets involved in T cell and NK cell differentiation and/or in the immune cell tumor-induced stress response with the aim of producing anti-tumor adoptive cell therapy grafts with improved functionality and persistence.
This work will expand on the recently published results from the Kiessling group demonstrating that an sd-rxRNA targeting PD-1 can enhance TIL antitumor activity against melanoma cells in vitro, further showing that ex vivotreatment with the sd-rxRNA compounds was easily incorporated into a clinically relevant rapid expansion protocol for TILs.1
Dr. Gerrit Dispersyn, chief development officer of RXi Pharmaceuticals, stated, “The combination of their prior results and the anticipated research results from this new collaboration are critical elements for a rapid advancement of sd-rxRNA immuno-oncology therapeutics into the clinic, further supported by our prior clinical experience with sd-rxRNA in other indications.”
Rolf Kiessling, MD, PhD, senior professor in Experimental Oncology at the Karolinska Institutet, senior chief physician at the Oncology clinic at the Karolinska University Hospital, and member of RXi’s Scientific Advisory Board stated, “Our results to date provide direct clinical relevance for the use of sd-rxRNA technology to improve ACT. In this collaboration, we look forward to exploring using sd-rxRNA to modulate targets outside of checkpoints to improve efficacy of immune effector cells such as T cells and NK cells.”
Immunotherapy of cancer has become increasingly important in clinical practice over the recent decade. By activating the patient’s immune system, immunotherapy treatments have shown remarkable promise in extending the lifespan of previously untreatable cancer patients. Adoptive cell therapy is an emerging immunotherapy approach which uses immune cells, such as T-lymphocytes or NK cells that are isolated from the patient or retrieved from allogeneic immune cell banks, and then expanded and in some cases processed to express tumor-binding receptors.
A new and important step in this ex-vivo processing of the immune cells is in development where self-delivering RNAi compounds are used to eliminate the expression of immunosuppressive receptors or proteins from the therapeutic immune cells, thereby making them less sensitive to tumor resistance mechanisms and improving their ability to destroy tumor cells. In this way, sd-rxRNA therapeutic compounds can be used to weaponize therapeutic immune cells to attack cancer and ultimately provide patients battling terminal cancers with a powerful new treatment option that goes beyond current treatment modalities.
1Ligtenberg et al., Self-Delivering RNAi Targeting PD-1 Improves Tumor-Specific T Cell Functionality for Adoptive Cell Therapy of Malignant Melanoma, Molecular Therapy, Vol. 26 No 6 June 2018.
(Source: RXi Pharmaceuticals Corporation)
Filed Under: Oncology